FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Next-Generation Sequencing Based Approach to Identify Underlying Genetic Defects of Glanzmann Thrombasthenia

Glanzmann thrombasthenia (GT) is an autosomal recessive platelet function disorder characterized by mucocutaneous bleeding as the most common clinical phenotype. Patients with GT have normal platelet counts, platelet morphology but reduced platelet aggregation in response to various agonists. Homozygosity or compound heterozygosity for variants in the ITGA2B/ITGB3 genes is the genetic basis for GT. Establishing a molecular diagnosis is definitive and is important for predictive testing. Using multi-gene panels is an accurate, faster, and cost-effective mode as compared to Sanger sequencing in large genes. We used a targeted resequencing based approach to identify pathogenic variants in eight cases in seven families. These variants were validated using Sanger sequencing in patients as well as family members and were predicted probably pathogenic using in-silico prediction tools. The variants include three missense (3/7 = 43%) (ITGA2B:c.1028 T > C, ITGA2B:c.1186G > A, ITGB3:c.1388G > C), two deletions (ITGA2B:c.559delG, ITGA2B:c.3092delT), one duplication (ITGA2B:c.1424_1427dupAGGT) and nonsense variant (ITGA2B:c.2578C > T, p.Gln860Ter). Except for one case which was compound heterozygous, the rest of the cases were homozygous. We found two novel variants that are reported for the first time in GT. The targeted resequencing based approach revealed varied genetic variants in North Indian patients, including two novels ones. The high yield of our panel indicates its suitability for usage in larger cohorts for the genetic diagnosis of GT patients. This approach is cost-effective and less cumbersome as compared to Sanger sequencing for these large size genes with multiple exons. The information so obtained is helpful in prenatal testing, carrier analysis, and genetic counseling.     

Update on ocular graft-versus-host disease

Ocular graft-versus-host disease (oGVHD) occurs as a complication following hematopoietic stem cell transplantation and is associated with significant ocular morbidity resulting in a marked reduction in the quality of life. With no current consensus on treatment protocols, management becomes challenging as recurrent oGVHD often refractory to conventional treatment. Most authors now diagnose and grade the disease based on criteria provided by the National Institutes of Health Consensus Conference (NIH CC) or the International Chronic oGVHD (ICCGVHD) consensus group. This article will provide an insight into the diagnostic criteria of oGVHD, its classification, and clinical severity grading scales. The inflammatory process in oGVHD can involve the entire ocular surface including the eyelids, meibomian gland, corneal, conjunctiva, and lacrimal system. The varied clinical presentations and treatment strategies employed to manage them have been discussed in the present study. The recent advances in ocular surface imaging in oGVHD patients such as the use of meibography and in vivo confocal microscopy may help in early diagnosis and prognostication of the disease. Researching tear proteomics and identification of novel potential tear biomarkers in oGVHD patients is an exciting field as they may help in objectively diagnosing the disease and monitoring the response to treatment.     

Intralenticular changes in eyes with mature senile cataract on modified posterior segment optical coherence tomography

Purpose:To study the morphological changes within mature senile cataracts on modified posterior segment optical coherence tomography (OCT).Methods:A cross-sectional observational study recruiting patients of mature cataracts admitted for elective cataract surgery in tertiary eye care. A modified OCT imaging of the lens was done and lenticular findings were noted by a single observer. Corresponding slit-lamp biomicroscopic findings and intraoperative experiences were also noted by a second observer and respective surgeons.Results:Forty-four eyes of 44 patients were included. The mean age of patients was 65 ± 5.7 years. The intralenticular findings were uniform in groups of eyes, and they were characterized into three stages. First was a stage of early lamellar separation where small intralenticular clefts were noted superficially. Second was the stage of established lamellar separation where crescentic fluid clefts appeared interspersed between the lens fibers, and the depth increased as a function of severity. Both these stages did not show any distinct slit-lamp or intraoperative findings. A third stage of liquefaction identified as extensive lamellar separation with subcapsular fluid pockets. This was also reflected in slit-lamp biomicroscopy, showing the hydrated cortex with intraoperative challenges. Two cases showed peculiar changes, one of a hyperreflective subcapsular sheath and another of superficial nuclear lamellar separation.Conclusion:Mature cataracts may also show graded progression, which could be delineated on lenticular OCT. This could be of immense help in pre-operative planning and optimal management of these high-risk cases.     

Efficacy of topical cyclosporine 0.05% and osmoprotective lubricating eye drops in treating dry eye disease and inflammation

Purpose:To evaluate the effect of topical cyclosporine 0.05% and osmoprotective lubricating eye drops on patients with dry eye disease (DED) with inflammation as measured by raised tear matrix metalloproteinases (MMP-9).Methods:This prospective study included 106 eyes of 53 patients diagnosed with DED based on any of the following DED criteria (Ocular Surface Disease Index [OSDI] score >12, tear film breakup time [TBUT] <10 s, Schirmer’s I test result <10 mm/5 min, ocular surface staining). Ocular surface inflammation was assessed by assessing MMP-9 positivity from tears of the patients in the study (Inflammadry kit Quidel corporation). Patients were prescribed osmoprotective lubricating eye drops (Osmodrops, Cipla Ltd) four times a day and cyclosporine A 0.05% eye drops (Imudrops, Cipla Ltd) twice a day for 6 months. Efficacy of the formulations was evaluated by OSDI scores, Schirmer’s test, TBUT change, reduction in ocular surface staining, and reduction in MMP-9 levels after 6 months of usage. Check P value and add from resultsResults:After 6 months of topical therapy, improvement was observed in OSDI scores (mean pretreatment: 25.7 ± 12.8, and mean posttreatment: 15.2 ± 8.4), P < 0.001. There was also reduction number of patients who were MMP-9 positive. Out of 75 eyes that tested MMP-9 positive, 70.66% showed reduction in MMP-9 levels P < 0.0001). Ocular surface staining also improved.Conclusion:Topical osmoprotective lubricating eye drops and cyclosporine A 0.05% reduce inflammation in cases of DED, which correlates with improvement in OSDI scores, ocular surface staining, and reduction in inflammation as measured by levels of tear MMP-9.     

Case series of volar juvenile xanthogranuloma: Clinical observation of a peripheral rim of hyperkeratosis

Juvenile xanthogranuloma is a benign histiocytic tumor predominantly occurring in children as yellowish papules on the head and trunk. Presentations on the volar surfaces are rare and may cause diagnostic confusion with pyogenic granuloma, eccrine poroma and digital fibrokeratoma. We report two patients with unusual presentations of solitary juvenile xanthogranuloma on the palm or sole. Both had lesions lacking the classic yellowish color and demonstrating a well‐defined, peripheral hyperkeratotic rim. Histopathological evaluation revealed prominent orthokeratosis corresponding to the rim. Additional histological features, including dermal histiocytes and Touton giant cells, were consistent with the diagnosis of juvenile xanthogranuloma. Given the unusual locations and colors of the lesions, we conclude that histopathological evaluation is central to diagnosing volar juvenile xanthogranuloma. We additionally suggest that juvenile xanthogranuloma should be included in the differential diagnoses of volar lesions displaying a peripheral hyperkeratotic rim.     

Ocular alterations in patients of alopecia areata

There is paucity of published work on ocular alterations in patients of alopecia areata (AA), especially from the Asian continent. We studied the clinical profile of 83 patients of AA and 80 sex- and age-matched controls to assess and compare the ocular changes, namely punctate opacities, cataract, intraocular tension and retinal changes. The outcome was analyzed with respect to prevalence of atopy, concomitant personal or family history of autoimmune diseases and nail changes in both the groups. The prevalence of atopy and family history of autoimmune diseases was significantly higher in the patient group. Lenticular changes were observed in 40.9% patients (including cataract in 16.9%) and 11.2% controls ( P  < 0.005). Within the patient group, lenticular involvement occurred with increased frequency in atopics ( P  = 0.034) and in the presence of family history of autoimmune diseases ( P  < 0.05). Retinal changes in the form of degenerative changes, pigmentary clumping and abnormal vascular changes were more prevalent ( P  < 0.001) in the study group. As the ocular changes were not found to correlate with the age, severity or extent of the disease, an initial ophthalmological screening of all patients is suggested.