Pre-operative optical coherence tomography predictors: Do they hold any relevance in the era of inverted internal limiting membrane flap in large macular holes?

Purpose: To study the relevance of preoperative OCT predictors in large macular holes (MH) treated using the inverted ILM peel technique. Methods: Prospective study of 95 patients undergoing vitrectomy for large MH between January 2019 and December 2020 was performed by dividing the patients into groups depending on various quantitative parameters and indices of MH such as base diameter (BD), hole form factor (HFF), macular hole index (MHI), diameter hole index (DHI), and tractional hole index (THI) by using parameters such as minimal hole diameter, hole height, nasal and temporal arm lengths. Depending upon the duration of symptoms, patients were divided into three groups: <3 months, 3–6 months, and >6 months. Anatomical success rate, type of closure, and postoperative vision gain were analyzed in relation to the abovementioned diameters, indices, and duration to see if any significance existed. Results: The mean age of patients included in the study was 60.48 ± 13.88 years, with female preponderance (males: females = 37:58). Change in logMAR was statistically significant individually with all studied parameters (P < 0.0001) without influence of size of hole and other indices. BD and DHI levels showed significant association with type of closure as indicated by P values of 0.017 and 0.048, respectively. Duration of symptoms showed no significance in terms of anatomical and functional success. Conclusion: OCT predictors of MH success seem to have lost relevance with inverted flap surgeries as 100% anatomical success is achieved with this technique, with 95.78% (91/95) achieving type 1 closure with statistically significant equivalent functional gain across the indices with no effect of duration of symptoms.

Reverse Swiss Roll technique for diabetic vitreous membranes

Background: Diabetic membranes are always a challenge for a surgeon because of sticky nature and chances of iatrogenic break while removing. Purpose: To demonstrate a safe reverse swiss roll technique to dissect diabetic vitreous membranes. Synposis: Approaches and techniques for membrane dissection are segmentation, delamination and en-bloc dissection using various types of instruments and illumination. With vitreous cutte, picks and scissors, surgical steps are traditionallu performed by using classic lift and shave technique. After identifying the plane, tissue is lifted and then cut, which puts the retina at risk of break because of traction and active suction. Such a threat can be reduced by placing the cutter above the membrane thereby having the membrane itseld acting as a protective cushion to the retina. Port here, unlike lift and shave technique, doesn抰 face the edge of membrane but is exactly 180 degree opposite and membrane curls into port because of suction. Also, hemostasis is maintained by continuous aspiration and cutting as the instrument is moved side to side, retracting from the edge. Highlights: Reverse swiss roll technique is safer compared to lift and shave because of the safety cushion of the membrane between the port and the retina. There is inherently less chances of retinal break because the active suction from the port is directed away from the retina. The technique also minimises traction and localised pull on the atrophic macula

Hypobaric hypoxia-mediated protein expression in plasma of susceptible & tolerant rats.

Background & objectives: Low availability of oxygen at high altitudes has a great impact on the human life processes. There is a widespread interest and need to find out protein(s) that are possibly involved in mediating tolerance to hypobaric hypoxia. We undertook this study to identify and characterize protein expression in plasma of hypoxia susceptible and tolerant rats. Methods: Male albino Sprague Dawley rats were segregated into susceptible and tolerant groups on the basis of their gasping time when exposed to simulated hypobaric hypoxia of 32,000 ft (9,754 m) at 32ºC. Comparative proteome profiling of blood plasma of hypoxia susceptible and tolerant individuals was performed using 2-dimentional (2-D) gel electrophoresis. Results: Three proteins with higher expression levels were selected separately from tolerant and susceptible samples. Characterization of these proteins from tolerant sample using MALDI-TOF/TOF and MASCOT search indicated their homology with two different super-families viz. NADB-Rossmann superfamily (Rab GDP dissociation inhibitor β) and Transferrin superfamily (two Serotransferrins), having potential role in imparting tolerance against hypoxia. Three high level upregulated proteins were characterized from blood plasma of hypoxia susceptible animals showing similarity with threonine tRNA ligase (mitochondrial), carbohydrate sulphotransferase 7 and aspartate tRNA ligase (cytoplasmic) that play a role in ATP binding, carbohydrate metabolism and protein biosynthesis, respectively. Interpretation & conclusions: Our results indicated that rats segregated into hypoxia sensitive and tolerant based on their gasping time showed differential expression of proteins in blood plasma. Characterization of these differentially expressed proteins will lead to better understanding of molecular responses occurring during hypoxia and subsequently development of biomarkers for categorization of hypoxia susceptible and tolerant individuals.

Implication of DNA repair genes in prostate tumourigenesis in Indian males.

Background & objectives: Prostate cancer (CaP) is the fifth most common cancer among Indian men. Tumour protein p53 (TP53) gene increases the fidelity of DNA replication and homologous recombination by transcriptional transactivation of mismatch repair (MMR) genes. DNA repair thus has a potential role in molecular carcinogenesis of CaP. The aim of the present study was to identify mutations, and polymorphisms in TP53 gene and MMR protein expression in CaP in Indian male population. Methods: TP53 codon 72 polymorphism was analysed in 105 CaP, 120 benign prostatic hyperplasia (BPH) cases and 106 normal controls. Mutational analysis of TP53 was done in DNA extracted from formalin fixed paraffin embedded tissue of 80 CaP and 24 BPH cases. Expression of MMR proteins viz. hMLH1, hMSH2, hPMS1 and hPMS2 was studied in 80 CaP, 15 prostatic intraepithelial neoplasia (PIN) and 15 BPH cases. Results: A somatic C/A variation at the intronic boundary of exon 7 in TP53 gene was observed in one each biopsy samples from CaP and BPH. A significant association of codon 72 TP53 Pro/Pro genotype was observed with the risk of CaP (OR, 2.59, P=0.02) and BPH (OR, 6.27, P<0.001). Immunohistochemical analysis of MMR proteins showed maximum loss of hPMS1 expression in cases of CaP and PIN while no loss in expression of MMR proteins was observed in BPH cases. The study also identified a significant loss of hPMS2 protein in poorly differentiated tumours (Gleason score >7) than in well differentiated tumours (Gleason score 3-6) (P<0.05). Interpretation & conclusions: The results of the present study demonstrate that TP53 codon 72 polymorphism plays significant role in the pathogenesis and susceptibility to CaP and BPH. Also, an aberrant MMR protein expression could be involved in progression of prostate cancer through PIN, early CaP to aggressive CaP. The loss of hPMS2 protein expression may serve as a marker for progression of CaP.

Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors.

Background & objectives: Breast cancer is the second most common malignancy in Indian women. Among the members of the steroid receptor superfamily the role of estrogen and progesterone receptors (ER and PR) is well established in breast cancer in predicting the prognosis and management of therapy, however, little is known about the clinical significance of androgen receptor (AR) in breast carcinogenesis. The present study was aimed to evaluate the expression of AR in breast cancer and to elucidate its clinical significance by correlating it with clinicopathological parameters, other steroid receptors (ER and PR) and growth factors receptors (EGFR and CD105). Methods: Expression of AR, ER, PR, epidermal growth factor receptor (EGFR) and endoglin (CD105) was studied in 100 cases of breast cancer by immunohistochemistry (IHC). Risk ratio (RR) along with 95% confidence interval (CI) was estimated to assess the strength of association between the markers and clinicopathological characteristics. Categorical principal component analysis (CATPCA) was applied to obtain new sets of linearly combined expression, for their further evaluation with clinicopathological characteristics (n=100). Results: In 31 cases presenting with locally advanced breast cancer (LABC), the expression of AR, ER, PR, EGFR and CD105 was associated with response to neoadjuvant chemotherapy (NACT). The results indicated the association of AR+ (P=0.001) and AR+/EGFR- (P=0.001) with the therapeutic response to NACT in LABC patients. The AR expression exhibited maximum sensitivity, specificity and likelihood ratio of positive and negative test. The present results showed the benefit of adding AR, EGFR and CD105 to the existing panel of markers to be able to predict response to therapy. Interpretation & conclusions: More studies on the expression profiles of AR+, AR+/CD105+ and AR+/EGFR- in larger set of breast cancer patients may possibly help in confirming their predictive role for therapeutic response in LABC patients.

Metaplastic carcinoma of the breast--a rare breast tumour.

Malignant breast neoplasms consisting of mixtures of epithelial and mesenchymal elements, are a rarity. Pathogenesis of such diverse elements within obviously infiltrating carcinomas has been the subject of much controversy. After the advent of immunohistochemistry, it is now generally accepted that metaplasia of the epithelial elements of a carcinoma gives these lesions their pseudosarcomatous appearance. Hence the name metaplastic carcinoma is given to malignant breast neoplasms which show Cytokeratin positivity in both epithelial and mesenchymal elements. We recently encountered such a case, which is being presented here along with relevant review of literature.