Does Multimodal Treatment Improve Eye and Life Salvage in Adenoid Cystic Carcinoma of the Lacrimal Gland?

PURPOSE: To evaluate the efficacy of multimodal treatment in adenoid cystic carcinoma (ACC) of the lacrimal gland. METHODS: A retrospective comparative case series of 40 consecutive patients with ACC of the lacrimal gland without systemic metastasis at the initial presentation and primarily managed by one of the 3 treatment protocols-surgery + external beam radiotherapy (EBRT) (group 1), surgery + EBRT + adjuvant chemotherapy (group 2), and neoadjuvant chemotherapy + surgery + EBRT + adjuvant chemotherapy (multimodal treatment) (group 3) at a tertiary care ocular oncology center. Local tumor control, eye salvage, and systemic metastasis were the primary outcome measures. RESULTS: The age ranged from 11 to 72 (mean ± SD, 36 ± 13; median, 36) years with 26 (65%) male and 14 (35%) female patients. Twelve (30%) patients belonged to group 1, 8 (20%) to group 2, and 20 (50%) to group 3. Primary surgery included tumor excision in 36 (90%) and orbital exenteration in 4 (10%). Chemotherapy composed of cisplatin + 5 fluorouracil (5FU) for 6 cycles in 28 (70%) patients. Extended-field stereotactic EBRT with a dose of 5,000-6,000 cGy included the entire pretreatment extent of the tumor with a 10-mm margin all around, superior orbital fissure, inferior orbital fissure, cavernous sinus, and temporal fossa. Mean duration of follow up after completion of treatment was 58 ± 26 (range, 29-180; median, 60) months. In all, local tumor recurrence occurred in 10 (25%) patients at a mean of 38 ± 23 (range, 12-120; median, 24) months. Local tumor recurrence was noted in 5 (42%) patients in group 1, 2 (25%) in group 2, and 3 (15%) in group 3. Overall, eye salvage was possible in 34 (85%) patients, with visual acuity >20/40 in 28 (82%). Systemic metastasis occurred in 10 (25%) patients at a mean of 53 ± 28 (range, 12-120; median, 43) months. Eight (67%) patients in group 1, 1 (13%) in group 2, and 1 (5%) in group 3 developed systemic metastasis. Six (15%) overall, 5 (42%) in group 1 and 1 (13%) in group 2, died with systemic metastasis. CONCLUSIONS: Multimodal treatment with sequential neoadjuvant chemotherapy, followed by surgery, extended-field stereotactic EBRT, and adjuvant chemotherapy seems relatively more effective in providing local tumor control and eye salvage and in minimizing the risk of systemic metastasis in ACC of the lacrimal gland.

Status and Interrelationship of Zinc, Copper, Iron, Calcium and Selenium in Prostate Cancer.

Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann-Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis.

Localized surgical debridement for the management of orbital mucormycosis.

PURPOSE: To describe the role of localized debridement and instillation of amphotericin B for the management of orbital mucormycosis post COVID-19 infection with a view to avoid exenteration. METHODS: The records of all patients with orbital mucormycosis post COVID-19 infection in the last 6 months from December 2020 to June 2021 were evaluated, and ten patients were identified who were successfully managed with localized debridement, that is, removing the fungal tissue and necrotic material and amphotericin B gel instillation locally. MRI scan was used to identify the area of fungal infiltration and presence of necrotic material. Early surgery in the form of transconjunctival orbitotomy was performed for disease in the infraorbital fissure area, and superior transcutaneous lid crease approach was employed for disease in the superomedial orbit or medial orbit. Most patients had lid edema, ptosis, and proptosis; this resolved with the medication. Systemic antifungals were given and the follow-up ranged from 1 to 5 months. RESULTS: The ptosis, proptosis, and lid edema subsided in all, except in one patient who had residual ptosis and in one who had residual ophthalmoplegia. Vision deficit did not occur in any patient. All patients were successfully discharged on oral antifungal medication. CONCLUSION: Localized clearance of the fungal tissue and the necrotic material is a good option to avoid exenteration in cases of orbital mucormycosis, avoiding disfigurement and mental trauma to the patient.

Retrobulbar injection of amphotericin B using intravenous cannula for post-COVID-19 rhino-orbital mucormycosis.

Rhino-orbital mucormycosis has seen a huge resurgence in patients post COVID-19 infection. In patients with minimal orbital disease and especially with preserved vision, retrobulbar injections of amphotericin B can be of great help in controlling the disease. Instead of giving daily injections of amphotericin B using needles every time, we used an 18-gauge intravenous (IV) cannula with injection port and suture holes to deliver the amphotericin into the orbital space for a period of 5 days. Patients were more compliant and less distressed with this method compared with being given an injection with a needle daily. We got a good response in terms of orbital disease regression with this method. In our review of the literature, we did not come across any such case of amphotericin B injection using an IV cannula. Injection of amphotericin B into the orbit using an IV cannula is a viable and easy treatment option for cases of rhino-orbital mucormycosis.

Custom ocular prosthesis in children: how often is a change required?

PURPOSE: To evaluate the indications, outcome and replacement schedule of custom ocular prostheses (COP) in children. METHODS: Retrospective review evaluating indications, outcome and replacement schedule of COP in children (≤16 years). RESULTS: Three hundred and thirty (330) children were fitted with COP. With average follow-up of 18.05 months (range 1-50 months), 136(41.2%) children needed replacement/modification of the prosthesis. Information regarding indications for replacement/modification of prosthesis was available in 125 cases. Indications included enophthalmic prosthesis in 34(27.2%), prosthesis rotation within the socket in 25(20%), loose fit in 16(12.8%), decentration of the cornea in 15(12%), color touch up in 13(10.4%), lost prosthesis in 8(6.4%), cosmetically significant ptosis in 2(1.6%), replacement following implant exchange surgery in 2(1.6%) and combination of above factors in 10(8%). Time for replacement/modification of prosthesis was assessed in 3 age groups. In ≤3 years, 47% (36 out of 76) children underwent replacement/modification at a mean duration of 18 months (range 3-39 months) from the date of prosthesis fitting. In the 3-12 years age group, 43% (80 out of 184) underwent replacement/modification at 21 months (range 2-48 months); and in the 12-16 year age group, 29% (20 out of 70) underwent replacement/modification of prosthesis at a mean duration of 26 months (range 3-50 months). CONCLUSION: A change of prosthesis is required between 18-26 months following prosthesis placement in children. Over an average of 18 months, a change in the prosthesis was required in 41%, with the youngest age group having the highest exchange rate (47%), and the oldest group the lowest (29%).

Inhalable particles containing isoniazid and rifabutin as adjunct therapy for safe, efficacious and relapse-free cure of experimental animal tuberculosis in one month.

We investigated the preclinical efficacy and safety/tolerability of biodegradable polymeric particles containing isoniazid (INH) and rifabutin (RFB) dry powder for inhalation (DPI) as an adjunct to oral first-line therapy. Mice and guinea pigs infected with Mycobacterium tuberculosis H37Rv (Mtb) were treated with ∼80 and ∼300 µg of the DPI, respectively, for 3-4 weeks starting 3, 10, and 30 days post-infection. Adjunct combination therapy eliminated culturable Mtb from the lungs and spleens of all but one of 52 animals that received the DPI. Relapse-free cure was not achieved in one mouse that received DPI + oral, human-equivalent doses (HED) of four drugs used in the Directly Observed Treatment, Short Course (DOTS), starting 30 days post-infection. Oral doses (20 mg/Kg/day, each) of INH + RFB reduced Mtb burden from ∼106 to ∼103 colony-forming units. Combining half the oral dose with DPI prevented relapse of infection four weeks after stopping the treatment. The DPI was safe in rodents, guinea pigs, and monkeys at 1, 10, and 100 µg/day doses over 90 days. In conclusion, we show the efficacy and safety/tolerability of the DPI as an adjunct to oral chemotherapy in three different animal models of TB.

Effects of drought and changes in vapour pressure deficit on water relations of Populus deltoides growing in ambient and elevated CO2.

The means by which growth CO(2) concentration ([CO(2)]) affects anatomy and water relations responses to drought and vapour pressure deficit (VPD) were studied for yearly coppiced, 4-year-old Populus deltoides clones that were grown in either 400 mumol mol(-1) (ambient) or 800 mumol mol(-1) (elevated) CO(2) for 3 years. It was hypothesized that, during drought, trees growing in elevated [CO(2)] would have a lower volume flux density of water (J(V)), stomatal conductance (g(s)) and transpiration per leaf area (E), as well as a lower stomatal density and a greater stomatal response to drought and changes in VPD than would trees in ambient [CO(2)]. Trees in elevated [CO(2)] actually had higher J(V) values throughout the study, but did not differ from trees in ambient [CO(2)] with respect to g(s) or E under saturating light or E scaled from J(V) (E(scaled)), all of which indicates that the higher J(V) in elevated [CO(2)] resulted from those trees having greater leaf area and not from differences in g(s). Furthermore, although plants in elevated [CO(2)] had greater absolute leaf loss during the drought, the percentage of leaf area lost was similar to that of trees in ambient [CO(2)]. g(s) and E under saturating light were affected by changes in VPD after the first 9 days of the experiment, which coincided with a large decrease in water potential at a soil depth of 0.1 m. Trees in elevated [CO(2)] had a greater stomatal density and a lower wood density than trees in ambient [CO(2)], both traits that may make the trees more susceptible to xylem cavitation in severe drought. Drought and VPD effects for the P. deltoides clone were not ameliorated by long-term growth in elevated [CO(2)] compared with ambient [CO(2)], and plants in elevated [CO(2)] possessed anatomical traits that may result in greater stress associated with long-term drought.

Quantitative evaluation of benzene, toluene, and xylene in the larvae of Drosophila melanogaster by solid-phase microextraction/gas chromatography/mass spectrometry for potential use in toxicological studies.

A simple, rapid, and solvent-free method for quantitative determination of benzene, toluene, and Xylene in exposed Drosophila larvae was developed using headspace solid-phase microextraction (HS-SPME) coupled to GC/MS. Larvae fed on standard Drosophila food mixed with benzene, toluene, and Xylene for 48 h were homogenized in Milli-Q water. Extraction of benzene, toluene, and Xylene was performed at 65 degrees C for 30 min on the SPME fiber (silica-fused). Subsequently, the fiber was desorbed in the GC injection port, followed by GC/MS analysis in the selected-ion monitoring mode. An external calibration curve was used for the quantification of benzene, toluene, and Xylene in the exposed organism. Recoveries were in the range of 78-82% (intraday) and 76-81% (interday) in larvae, and 91-96% (intraday) and 87-92% (interday) in the diet. LOD with an S/N of 3:1 and LOQ with an S/N of 10:1 were in the range of 0.01-0.023 and 0.034-0.077 microg/L, respectively. Percent RSD values for benzene, toluene, and Xylene were in the range of 0.50-0.81 (intraday) and 0.89-1.23 (interday) for retention time, and 2.16--3.85 (intraday) and 2.99-4.95 (interday) for peak concentration, showing good repeatability. This method was sensitive enough to quantitate benzene, toluene, and Xylene in small exposed organisms like Drosophila larvae. The SPME/GC/MS method developed may have wider applications in various in vivo toxicological studies.

Centurion syndrome: clinical presentation and surgical outcome.

PURPOSE: To describe the clinical signs and outcome of surgery in cases with Centurion syndrome and highlight the clinical presentation of this syndrome. METHODS: A retrospective review of records of patients with Centurion syndrome who underwent surgery between January 2002 and July 2007. The position of the punctum, nasal bridge prominence, Hertel exophthalmometry and the presence of inferiorly directed sharp angulation of the medial canthus was noted. The patients underwent anterior canthal tendon release, punctoplasty or medial conjunctivoplasty or a combination of these. RESULTS: Of the 13 cases, 10 had been treated medically elsewhere. The mean age of onset was 20.7 years. Most of the patients were male 10 (76.9%). A prominent nasal bridge was demonstrable in 9 (69.2%) patients and sharp inferior angulation of the medial canthus, the 'beak' sign was present in 9 (69.2%) cases. Anterior canthal tendon release alone was performed in 4 patients, in combination with punctoplasty in 5 and with conjunctivoplasty in 4. Watering resolved in 10 patients. 3 patients who had a combination of anterior canthal tendon release and punctoplasty had persistent but asymptomatic epiphora. DISCUSSION: Centurion syndrome is characterised by the abnormal anterior insertion of the medial canthal tendon with displacement of the punctum out of the lacrimal lake. Most cases present with unexplained watering. Surgical management by anterior canthal tendon release with or without conjunctivoplasty or lower lid retractor plication is usually successful.

Sebaceous carcinoma of the eyelid metastasizing to the lacrimal sac after 5 years.

Eyelid sebaceous carcinoma metastasizing to lacrimal sac is rare. A 65 year old female underwent excision with 5 mm margins and Cutler-beard reconstruction for a nodulo-ulcerative mass showing eyelash loss in the middle third of the right upper eyelid. Histopathology confirmed it to be sebaceous carcinoma with uninvolved margins. Five years after primary excision, the patient presented with persistent epiphora and mass in the ipsilateral lacrimal sac region. Repeat excision biopsy and conjunctival map biopsy confirmed recurrent sebaceous carcinoma of the lacrimal sac. Thirteen months after adjuvant radiotherapy to the orbit, the patient is alive and well with no loco-regional recurrence.

DNA damage induced by industrial solid waste leachates in Drosophila melanogaster: a mechanistic approach.

Genomic stability requires that error-free genetic information be transmitted from generation to generation, a process that is dependent upon efficient DNA repair. Industrial leachates which contain mixtures of diverse chemicals are a major environmental concern. The interaction between these chemicals may have synergistic, antagonistic, or simply additive effects on biological systems. In the present study, the Comet assay was used to measure the DNA damage produced by leachates of solid wastes from flashlight battery, pigment, and tanning factories in the midgut cells and brain ganglia of Drosophila melanogaster mutants deficient in DNA repair proteins. Larvae were allowed to feed for 48 or 72 hr on diets containing 0.1, 0.5, and 2.0% (v/v) of the leachates. Physicochemical analysis run on the solid wastes, leachates, and treated larvae detected elevated levels of heavy metals. Leachates produced significantly greater levels of DNA damage in mutant strains mei41 (deficient in cell cycle check point protein), mus201 (deficient in excision repair protein), mus308 (deficient in postreplication repair protein), and rad54 (deficient in double strand break repair protein) than in the OregonR(+) wild-type strain. Larvae of the ligaseIV mutant (deficient in double strand break repair protein) were hypersensitive only to the pigment plant waste leachate. Conversely, the dnase2 mutant (deficient in protein responsible for degrading fragmented DNA) was more sensitive to DNA damage induction from the flashlight battery and tannery waste leachates. Our data demonstrate that repair of DNA damage in organisms exposed to leachates is dependent upon several DNA repair proteins, indicative of the involvement of multiple overlapping repair pathways. The study further suggests the usefulness of the Comet assay for studying the mechanisms of DNA repair in Drosophila.

Lateral fixation of sclera to the periosteum with medial rectus disinsertion for severe myopic strabismus fixus.

Myopic strabismus fixus is characterized by severe ocular motility restriction with the development of progressive esotropia and hypotropia. Management of severe cases with strongly positive forced duction test can be challenging. We describe a longstanding case of myopic strabismus fixus, which was managed by bilateral medial rectus disinsertion and scleral fixation laterally to the periosteum.

Magnetic ocular prosthesis for shallow contracted socket.

Contracted sockets with poor retention of ocular prosthesis are difficult to manage especially when it is a dry socket. A 50-year-old lady with history of irradiation to the socket following enucleation for retinoblastoma reported to us with severe socket contracture, dry socket, and inadequate lid closure with a poorly retained ocular prosthesis. She was using a stone in the socket for support with a cracked stock ocular prosthesis placed over it. A two-piece ocular prosthesis was created with a base and shell with neodymium-boron-ferrous magnets in each part, with good retention and positioning, and this was cosmetically acceptable to the patient. To the best of our knowledge, this is the first report of such a two-piece magnetic ocular prosthesis.

DNA damage induced in human peripheral blood lymphocytes by industrial solid waste and municipal sludge leachates.

Exposure of humans to toxic compounds occurs mostly in the form of complex mixtures. Leachates, consisting of mixtures of many chemicals, are a potential risk to human health. In the present study, leachates of solid wastes from a polyfiber factory (PFL), an aeronautical plant (AEL), and a municipal sludge leachate (MSL) were assessed for their ability to induce DNA damage in human peripheral blood lymphocytes using the alkaline Comet assay. The leachates also were examined for their physical and chemical properties. Lymphocytes were incubated with 0.5-15.0% concentrations (pH range 7.1-7.4) of the test leachates for 3 hr at 37 degrees C, and treatment with 1 mM ethyl methanesulfonate served as a positive control. All three leachates induced significant (P < 0.05), concentration-dependent increases in DNA damage compared with the negative control, as measured by increases in Olive tail moment (arbitrary units), tail DNA (%), and tail length (mum). A comparison of these variables among the treatment groups indicated that the MSL induced the most DNA damage. Inductively coupled plasma emission spectrometry analysis of the leachates indicated that they contained high concentrations of heavy metals, viz. iron, manganese, nickel, zinc, cadmium, chromium, and lead. The individual, synergistic, or antagonistic effects of these chemicals in the leachates may be responsible for the DNA damage. Our data indicate that the ever-increasing amounts of leachates from waste landfill sites have the potential to induce DNA damage and suggest that the exposure of human populations to these leachates may lead to adverse health effects.

Induction of biochemical stress markers and apoptosis in transgenic Drosophila melanogaster against complex chemical mixtures: role of reactive oxygen species.

The study was aimed to investigate the effect of leachates of solid waste from a flashlight battery factory and a pigment plant on 70 kDa heat shock protein (Hsp70) expression, generation of reactive oxygen species (ROS), antioxidant enzymes activities and apoptosis in Drosophila. Third instar larvae of Drosophila melanogaster transgenic for hsp70 (hsp70-lacZ) were fed on diet mixed with leachates of solid wastes (0.05-2.0%, v/v) released from two industrial plants at three different pHs (7.00, 4.93 and 2.88) for 2-48 h. A concentration- and time-dependent significant change in Hsp70 expression, ROS generation, antioxidant enzymes activities and MDA content was observed in the exposed larvae preceding the antioxidant enzymes activities. Mitochondria-mediated, caspase-dependent apoptotic cell death in the larvae exposed to 1.0 and 2.0% leachates of flashlight battery factory was concurrent with a significant regression in Hsp70 expression and a higher ROS generation. A positive correlation drawn between ROS generation and apoptotic markers and a negative correlation between apoptotic markers and Hsp70 expression in these groups indicated the important role of ROS in the leachate-induced cellular damage. Hsp70 along with antioxidant enzymes offered protection to the organisms exposed to all the tested concentrations of the leachates of pigment plant waste and 0.5% leachate of flashlight battery factory in a cooperative manner when ROS generation was less induced. Conversely, higher levels of ROS generation in the organisms treated with 1.0 and 2.0% leachate of flashlight battery factory after 24 and 48 h resulted in regression of Hsp70 expression in them leading to cell death. The study suggests that (1) leachates of flashlight battery factory waste more adversely affected the organisms in comparison to the leachates of pigment plant waste. (2) Hsp70 may be used as a biomarker of cellular damage in organisms exposed to leachates. (3) Cell based assays using D. melanogaster as an in vivo model may provide important mechanistic information about the adverse effect of xenobiotics.

Unilateral restrictive ophthalmoplegia and enophthalmos associated with an intraorbital tissue band.

Fibrosis of the extraocular muscles can be congenital or acquired. Acquired causes include trauma, myositis, thyroid eye disease, infection, and metastases. Congenital fibrosis of the extraocular muscles (CFEOM) runs in families and is known to have a genetic basis. It has been classified by Brown, Hansen, and Harley et al into the five following types: general fibrosis syndrome; fibrosis of the inferior rectus (IR) with blepharoptosis; strabismus fixus; vertical retraction syndrome; and unilateral fibrosis, blepharoptosis, and enophthalmos syndrome. In this report, a case of unilateral fibrosis with enophthalmos and blepharoptosis due to a fibrous band is described.

Botulinum toxin in the management of internuclear ophthalmoplegia.

BACKGROUND: Internuclear ophthalmoplegia (INO) presents as a complex ocular motility problem due to medial longitudinal fasciculus damage. The symptoms are disabling and challenging to manage. We evaluate the efficacy of botulinum toxin in the management of INO. METHODS: A retrospective review of 16 patients with INO managed by botulinum toxin A injection into one or more extraocular muscles over the past 20 years was performed. The age, sex, etiology, symptoms, angle of deviation, and binocular function pre- and postinjection were analyzed. RESULTS: The mean age at presentation was 45.1 years with a male/female ratio of 9:7. The most common etiologies included brainstem hemorrhage in five and multiple sclerosis in four. After injection diplopia reduced in 14 (87.5%), appearance improved in 9 (56.3%), and the head posture improved in 4 (25%). Convergence recovered in two patients (12.5%) and stereopsis improved in three patients (18.8%). Complications included transient ptosis in one patient, and one patient had an overcorrection. Two patients complained of transient vertical diplopia that resolved within 3 weeks. At final follow-up, five (31.5%) patients continued on maintenance injections, three (18.8%) were stable and discharged, while the rest were managed by occlusion (five), prisms (one), or surgery (two). CONCLUSIONS: We report on the management of INO by botulinum toxin. Benefit was noted in terms of reduced diplopia and occasionally improved binocular function. Though the benefits are limited by the need for repeated injections, for patients with this debilitating condition, botulinum toxin provides some symptomatic relief.

Systemic metastasis following hyphema drainage in an unsuspected retinoblastoma.

A 6-year-old girl had total hyphema and elevated left intraocular pressure following trivial trauma. B-scan with vector A-scan revealed vitreous opacities consistent with hemorrhage. The drained hyphema did not recur. A left vascular conjunctival mass and massive cervical lymphadenopathy occurred 7 months later. Biopsy revealed extraocular retinoblastoma and lymph node metastasis. Computed tomography showed an intraocular mass with intracranial extension. She died of metastatic disease despite intensive chemotherapy. Retinoblastoma should be suspected in a child with hyphema following trivial trauma.

Amniotic membrane transplantation: a review of current indications in the management of ophthalmic disorders.

Amniotic membrane transplantation is currently being used for a continuously widening spectrum of ophthalmic indications. It has gained widespread attention as an effective method of reconstruction of the ocular surface. Amniotic membrane has a unique combination of properties, including the facilitation of migration of epithelial cells, the reinforcement of basal cellular adhesion and the encouragement of epithelial differentiation. Its ability to modulate stromal scarring and its anti-inflammatory activity has led to its use in the treatment of ocular surface pathology as well as an adjunct to limbal stem cell grafts. Amniotic membrane transplantation has been used for reconstruction of the corneal surface in the setting of persistent epithelial defects, partial limbal stem cell deficiency, bullous keratopathy and corneoscleral ulcers. It has also been used in conjunction with limbal stem cell transplantation for total limbal stem cell deficiency. Amniotic membrane grafts have been effectively used as a conjunctival substitute for reconstruction of conjunctival defects following removal of pterygia, conjunctival lesions and symblephara. More recently, amniotic membrane has been used as a substrate for ex vivo cultivation of limbal, corneal and conjunctival epithelial cells. This article reviews the current literature on the applications of amniotic membrane transplantation and its outcome in various ophthalmic conditions.