Voriconazole Induced Ocular Surface Dysplasia - Report of Two Cases.

PURPOSE: To report ocular surface dysplasia induced by voriconazole treatment in two patients with recalcitrant fungal keratitis. METHODS: Observational study. RESULTS: Case 1 - A 49 year old female who was a known case of fungal keratitis and treated with prolonged topical voriconazole therapy, underwent penetrating keratoplasty and the histopathological examination of corneal specimen showed multiple keratin pearls with dyskeratotic cells suggestive of squamous cell carcinoma.Case 2 - A 78-year-old man who was diagnosed as fungal keratitis in his left eye and treated with topical voriconazole 1% and itraconazole 1% for 6 months underwent therapeutic penetrating keratoplasty. Histopathology of the host corneal tissue showed squamous cells with irregular thickening with dyskeratotic cells and squamous eddies suggestive of voriconazole induced dysplasia. CONCLUSION: Prolonged topical voriconazole treatment in fungal keratitis can induce ocular surface dysplasia. Early diagnosis and treatment of the dysplastic changes can result in complete remission and prevent recurrence.

Structural insights on druggable hotspots in CD147: A bull's eye view.

CD147/Basigin/EMMPRIN (Extracellular Matrix Metalloproteinase inducer) is a single pass type1 transmembrane protein playing a central role in developmental process, wound healing, nutrient transport, inflammation, arthritis and also in microbial pathologies. It is also found to be a potent stimulator of MMP (matrix metalloproteinases) and has been considered as a prognostic marker in cancer. Dysregulation of CD147 is reported in several types of cancer. It activates cell proliferation, invasion, metastasis and inhibits tumor cell apoptosis under hypoxic condition. Thus, CD147 serves as a hub protein in cancer, as it is involved in several homophilic and heterophilic cellular interactions spanning the major hallmarks of cancer. Targeting these interactions is considered to be an efficient therapeutic modality in cancerous conditions. Hence, by this review we intend to collate the structure-function relationships of CD147, with an exclusive thrust on potential druggable hotspots based on its intra and inter molecular interactions.

Basal ganglia and autism - a translational perspective.

The basal ganglia are a collection of nuclei below the cortical surface that are involved in both motor and non-motor functions, including higher order cognition, social interactions, speech, and repetitive behaviors. Motor development milestones that are delayed in autism such as gross motor, fine motor and walking can aid in early diagnosis of autism. Neuropathology and neuroimaging findings in autism cases revealed volumetric changes and altered cell density in select basal ganglia nuclei. Interestingly, in autism, both the basal ganglia and the cerebellum are impacted both in their motor and non-motor domains and recently, found to be connected via the pons through a short disynaptic pathway. In typically developing individuals, the basal ganglia plays an important role in: eye movement, movement coordination, sensory modulation and processing, eye-hand coordination, action chaining, and inhibition control. Genetic models have proved to be useful toward understanding cellular and molecular changes at the synaptic level in the basal ganglia that may in part contribute to these autism-related behaviors. In autism, basal ganglia functions in motor skill acquisition and development are altered, thus disrupting the normal flow of feedback to the cortex. Taken together, there is an abundance of emerging evidence that the basal ganglia likely plays critical roles in maintaining an inhibitory balance between cortical and subcortical structures, critical for normal motor actions and cognitive functions. In autism, this inhibitory balance is disturbed thus impacting key pathways that affect normal cortical network activity. Autism Res 2017, 10: 1751-1775. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Habit learning, action selection and performance are modulated by the basal ganglia, a collection of groups of neurons located below the cerebral cortex in the brain. In autism, there is emerging evidence that parts of the basal ganglia are structurally and functionally altered disrupting normal information flow. The basal ganglia through its interconnected circuits with the cerebral cortex and the cerebellum can potentially impact various motor and cognitive functions in the autism brain.

Massive mycobacterial choroiditis during highly active antiretroviral therapy: another immune-recovery uveitis?

PURPOSE: To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS). STUDY DESIGN: Case report and literature review. PARTICIPANTS: A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis. METHODS: The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy. His left eye became blind and painful and was enucleated. Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas. Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC). RESULTS: Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate. Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued. One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease. CONCLUSIONS: This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease. Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection. The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism.