Validation of the Malayalam Version of Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale in Cancer Patients in the Regional Cancer Centre, Thiruvananthapuram, Kerala, India.

OBJECTIVE: The Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) is a 7-item self-report scale developed to identify pain which is of predominantly neuropathic origin. The aim of this study was to develop a Malayalam version of the LANSS and to test its validity and reliability in chronic pain patients. METHODOLOGY: We enrolled 101 Malayalam-speaking chronic pain patients who visited the Division of Palliative Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala, India. The translated version of S- LANSS was constructed by standard means. Fifty-one neuropathic pain and fifty nociceptive pain patients were identified by an independent pain physician and were subjected to the new pain scale by a palliative care nurse who was blinded to the diagnosis. The "gold standard diagnosis" is what the physician makes after clinical examination. Its validation, sensitivity, specificity, and positive and negative predictive values were determined. RESULTS: Fifty-one neuropathic pain and fifty nociceptive pain patients were subjected to the Malayalam version of S-LANSS pain scale for validity testing. The agreement by Cohen's Kappa 0.743, Chi-square test P < 0.001, sensitivity 89.58, specificity 84.91, positive predictive value 84.31, negative predictive value 90.00, accuracy by 87.13, and likelihood ratio 5.94. CONCLUSION: The Malayalam version of S-LANSS pain scale is a validated screening tool for identifying neuropathic pain in chronic pain patients in Malayalam-speaking regions.

Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity.

Antibiotics such as fluoroquinolones (FQLs) are commonly used to treat ocular infections but are also known to cause dermal melanocyte toxicity. The release of dispersed pigments from the iris into the aqueous humor has been considered a possible ocular side effect of the systemic administration of FQLs such as Moxifloxacin, and this condition is known as bilateral acute iris transillumination (BAIT). Bilateral acute depigmentation of iris (BADI) is a similar condition, with iris pigment released into the aqueous, but it has not been reported as a side effect of FQL. Iris pigments are synthesized by the melanogenic enzyme tyrosinase (TYR) and can be detected but not quantified by using slit-lamp biomicroscopy. The correlation between dispersed pigments in the aqueous and the extent of melanocyte toxicity due to topical antibiotics in vivo is not well studied. Here, we aimed to study the effect of topical FQLs on iris tissue, the pigment release in the aqueous humor and the development of clinically evident iris atrophic changes. We evaluated this process by measuring the activity of TYR in the aqueous humor of 82 healthy eyes undergoing cataract surgery following topical application of FQLs such as Moxifloxacin (27 eyes, preservative-free) or Ciprofloxacin (29 eyes, with preservative) or the application of non-FQL Tobramycin (26 eyes, with preservative) as a control. In addition, the patients were questioned and examined for ocular side effects in pre- and post-operative periods. Our data showed a significantly higher mean TYR activity in the aqueous humor of Ciprofloxacin-treated eyes compared to Moxifloxacin- (preservative free, p < 0.0001) or Tobramycin-treated eyes (p < 0.0001), which indicated that few quinolones under certain conditions are toxic to the iris melanocytes. However, the reduced TYR activity in the aqueous of Moxifloxacin-treated eyes was possibly due to the presence of a higher drug concentration, which inhibits TYR activity. Consistently, immunoblotting analysis of the aqueous humor from both Ciprofloxacin- and Moxifloxacin-treated eyes showed the presence of soluble TYR enzyme, thus reflecting its toxicity to iris melanocytes and corresponding to its activity in the aqueous humor. Intriguingly, none of these patients developed any clinically appreciable ocular side effects characteristic of BAIT or BADI. Overall, our results suggest that topical antibiotics cause different levels of iris melanocyte toxicity, releasing dispersed pigments into the aqueous humor, which can be measured through TYR enzyme activity. Hence, we conclude that topical FQLs may cause subclinical toxicity to the iris melanocytes but may not be the sole cause of the development of BAIT or BADI.

Noncontact Quantification of Topography of Anterior Corneal Surface and Bowman's Layer With High-Speed OCT.

PURPOSE: To quantify keratometry and wavefront aberration of the anterior corneal surface and epithelium-Bowman's layer interface using anterior segment optical coherence tomography (OCT). METHODS: Twenty-five normal eyes and 25 eyes with keratoconus were retrospectively analyzed. The anterior corneal edge and epithelium-Bowman's layer interface were segmented from 12 distortion-corrected OCT B-scans. Axial tangential curvatures and wavefront aberration were calculated by ray tracing and 6th order Zernike analyses. All eyes underwent simultaneous imaging with Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany). The Pentacam elevation data were used for aberration analyses using the same ray-tracing method. The paired t test was used to compare the variables. RESULTS: In normal eyes, mean steep axis and maximum keratometry of OCT of the anterior corneal surface and epithelium-Bowman's layer interface were significantly greater than the same of the Pentacam anterior corneal surface (P < .05). Mean root mean square of higher order aberrations of the OCT surfaces was greater than the same of the Pentacam surface by a factor of 4. In eyes with keratoconus, mean steep axis and maximum keratometry of the OCT epithelium-Bowman's layer interface was the greatest (P < .05). Mean root mean square of the higher order aberrations and vertical coma of the OCT epithelium-Bowman's layer interface was the greatest (P < .05). In general, the aberrations of the OCT epithelium-Bowman's layer interface were significantly greater than those of the Pentacam anterior corneal surface. CONCLUSIONS: A noncontact method to quantify the topography and aberrations of corneal surfaces with OCT was presented. OCT measurements yielded greater curvature and aberrations than Pentacam in both normal and keratoconic eyes. [J Refract Surg. 2017;33(5):330-336.].

Fetal-specific hypermethylated RASSF1A quantification in pregnancy.

OBJECTIVE: To quantify cell free fetal DNA (cffDNA) with fetal specific epigenetic marker, hypermethylated RASSF1A, in maternal plasma of normal pregnant women from 20 weeks of gestation and to assess its relationship with maternal age, height, pre-pregnancy weight and body mass index (BMI). METHODS: Hundred normal pregnant women within the gestational age of 21-40 weeks were randomly selected and grouped into five (n = 20). Group 1: 21-24, Group 2: 25-28, Group 3: 29-32, Group 4: 33-36 and Group 5: 37-40 weeks. Maternal plasma DNA was extracted, digested with methylation-sensitive restriction enzyme, BstUI and the fetal specific DNA (cffDNA) was quantified by Real-time polymerase chain reaction (qRT-PCR). RESULTS: The mean hypermethylated RASSF1A concentrations in different gestational groups were Group 1: 30.1 ± 14.9, Group 2: 52.6 ± 22.18, Group 3: 93.2 ± 19.08, Group 4: 172.8 ± 26.81 and Group 5: 337.8 ± 52.9 copies/ml. Pearson's correlation analysis showed highly significant positive correlation between cffDNA and gestational age (r = 0.899, p < 0.001). BMI was also found to be positively related to cffDNA (r = 0.217, p < 0.05). However, it did not show any correlation with maternal age, height and pre-pregnancy weight. CONCLUSIONS: The gestational age-dependent increase of hypermethylated RASSF1A; the fetal specific epigenetic marker in maternal plasma was demonstrated, in an Indian study group of normal pregnant women. Findings would form the basis of future studies involving pregnancy complications that would aid in the early diagnosis of placental pathologies with hypermethylated RASSF1A.

Evaluation of fetal hypermethylated RASSF1A in pre-eclampsia and its relationship with placental protein-13, pregnancy associated plasma protein-A and urine protein.

OBJECTIVES: Cell free fetal DNA (cffDNA) and its hypermethylated RASSF1A gene signify a recent advancement in non-invasive prenatal diagnosis of feto-placental anomalies like pre-eclampsia. The study uses hypermethylated RASSF1A gene to quantify cffDNA and to assess its relationship with placental and urine proteins in pre-eclampsia cases. DESIGN AND METHODS: DNA was isolated from plasma samples of clinically diagnosed cases of pre-eclampsia (n=103) and normal pregnancy (n=616) from 21weeks of gestation. Through methylation sensitive enzyme (BstUI) digestion; followed by real time-polymerase chain reaction (RT-PCR), quantification of hypermethylated RASSF1A was done. Immunoassays determined: placental protein-13 (pp-13) and pregnancy associated plasma protein A (PAPP-A) and pyrogallol red molybdate assay for 24h urine protein. RESULTS: Highly significant differences between control and pre-eclampsia cases for hypermethylated RASSF1A concentrations were found; Group I: 33±7.35 vs 74.46±16.71, Group II: 53.75±16.65 vs 244.22±35.68, Group III: 93.25±19.08 vs 412.31±80.18, Group IV: 144.30±18.13 vs 1056.89±153.78, Group V: 307.55±40.76 vs 2763.76±259.76copies/ml. Multivariate Pearson's correlation analysis of hypermethylated RASSF1A with pp-13, PAPP-A and urine proteins showed positive and very highly significant (P<0.001) associations. CONCLUSIONS: Diagnostic potential of fetal specific, hypermethylated RASSF1A was evaluated. Its positive relationship with placental and urine proteins submit the case for considering it as a reliable marker for pre-eclampsia.

Preclinical cataract masquerading as post-LASIK regression.

The purpose of this case report is to bring forth a rare clinical scenario where preclinical cataract mimics post-LASIK regression and to describe the role of aberrometry in detecting higher order aberrations (HOAs) and early lens changes. A 36-year-old female presented with blurring of vision since 1 year after having undergone an uneventful LASIK surgery 3 years prior. Corneal topography and aberrometry were within normal limits. Although the lens was morphologically normal on slit lamp examination, increased HOAs and lenticular density were detected. Since there were no cataractous changes, the patient was advised regular follow-up. A year later, the patient had developed lenticular changes along with a further increase in aberrations and worsening of scatter on densitometry. Increase in aberrations and lenticular density may serve as a marker for cataract development before clinically detectable lenticular changes. This report shows how preclinical cataract can mimic post-LASIK regression with a change in spherical and cylindrical power of the eye. This could result in patients undergoing re-correction in eyes where the primary pathology is in the lens.

Biometry with a new swept-source optical coherence tomography biometer: Repeatability and agreement with an optical low-coherence reflectometry device.

PURPOSE: To assess the repeatability of a new swept-source optical coherence tomography (SS-OCT) biometer (IOLMaster 700) and evaluate the agreement with an optical low-coherence reflectometry (OLCR) biometer (Lenstar 900) in cataractous eyes. SETTING: Tertiary eyecare facility. DESIGN: Prospective evaluation of a diagnostic test. METHODS: Eyes of patients had 3 consecutive scans acquired by the same operator. The repeatability of measurements was assessed using the within-subject standard deviation and coefficient of variation (CoV). Agreement between the mean measurements of each machine was evaluated. RESULTS: The study comprised 100 eyes of 100 patients. The median lens thickness and axial length (AL) measurements were significantly greater (P < .001) with SS-OCT (4.29 mm and 23.5 mm, respectively, versus 4.25 mm and 23.4 mm, respectively); anterior chamber depth (ACD) was greater with OLCR (2.72 mm versus 2.70 mm, respectively) (P < .001). The within-subject standard deviation and CoV of the AL (0.01 and 0.05, respectively) and the ACD (0.04 and 1.22, respectively) measurements showed lower variability with SS-OCT (0.05 and 0.21, respectively, for AL; 0.06 and 1.99, respectively, for ACD) than with OLCR. Good agreement was seen for anterior segment measurements between the 2 devices. The 95% limits of agreement of most parameters fell within the test-retest variability of the parameters. The SS-OCT biometer also showed better penetration in dense posterior subcapsular cataracts, measuring AL successfully in 96% of cases. CONCLUSIONS: The new SS-OCT biometer showed good repeatability and agreement with the OLCR biometer. The SS-OCT biometer measured the AL with fewer dropouts compared with the OLCR even in dense cataracts. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Macular edema in Asian Indian premature infants with retinopathy of prematurity: Impact on visual acuity and refractive status after 1-year.

PURPOSE: To report the impact of transient, self-resolving, untreated "macular edema" detected on spectral domain optical coherence tomography in Asian Indian premature infants with retinopathy of prematurity (ROP) on visual acuity (VA) and refraction at 1-year of corrected age. MATERIALS AND METHODS: Visual acuity and refraction of 11 infants with bilateral macular edema (Group A) was compared with gestational age-matched 16 infants with ROP without edema (Group B) and 17 preterms infants without ROP and without edema (Group C) at 3, 6, 9 and 12 months of corrected age using Teller Acuity Cards and cycloplegic retinoscopy. Sub-group analysis of the previously described pattern A and B macular edema was performed. RESULTS: Visual acuity was lower in infants with macular edema compared with the other two control groups throughout the study period, but statistically significant only at 3 months. Visual improvement in these infants was highest between the 3 rd and 6 th month and plateaued by the end of the 1 st year with acuity comparable to the other two groups. The edema cohort was more hyperopic compared to the other two groups between 3 and 12 months of age. Pattern A edema had worse VA compared to pattern B, although not statistically significant. CONCLUSION: Macular edema, although transient, caused reduced VA as early as 3 months of corrected age in Asian Indian premature infants weighing <2000 g at birth. The higher hyperopia in these infants is possibly due to visual disturbances caused at a critical time of fovealization. We hypothesize a recovery and feedback mechanism based on the principles of active emmetropization to explain our findings.

Effect of ion-implantation on surface characteristics of nickel titanium and titanium molybdenum alloy arch wires.

AIM: To evaluate the changes in surface roughness and frictional features of 'ion-implanted nickel titanium (NiTi) and titanium molybdenum alloy (TMA) arch wires' from its conventional types in an in-vitro laboratory set up. MATERIALS AND METHODS: 'Ion-implanted NiTi and low friction TMA arch wires' were assessed for surface roughness with scanning electron microscopy (SEM) and 3 dimensional (3D) optical profilometry. Frictional forces were studied in a universal testing machine. Surface roughness of arch wires were determined as Root Mean Square (RMS) values in nanometers and Frictional Forces (FF) in grams. STATISTICAL ANALYSIS USED: Mean values of RMS and FF were compared by Student's 't' test and one way analysis of variance (ANOVA). RESULTS: SEM images showed a smooth topography for ion-implanted versions. 3D optical profilometry demonstrated reduction of RMS values by 58.43% for ion-implanted NiTi (795.95 to 330.87 nm) and 48.90% for TMA groups (463.28 to 236.35 nm) from controls. Nonetheless, the corresponding decrease in FF was only 29.18% for NiTi and 22.04% for TMA, suggesting partial correction of surface roughness and disproportionate reduction in frictional forces with ion-implantation. Though the reductions were highly significant at P < 0.001, relations between surface roughness and frictional forces remained non conclusive even after ion-implantation. CONCLUSION: The study proved that ion-implantation can significantly reduce the surface roughness of NiTi and TMA wires but could not make a similar reduction in frictional forces. This can be attributed to the inherent differences in stiffness and surface reactivity of NiTi and TMA wires when used in combination with stainless steel brackets, which needs further investigations.

Y sign: clinical indicator to stop trenching and start cracking.

Phacoemulsification is challenging in soft cataracts due to the difficulty in cracking the nucleus by a divide-and-conquer technique or by chopping. We describe another technique, the Y sign for trenching endpoint: a clinical sign that indicates the surgeon should stop trenching and start cracking during classical divide-and-conquer nucleofractis emulsification using proximal downslope trenching. This technique exploits the morphological structure of the lens to precisely gauge the depth of the trench at which the surgeon can split even a soft nucleus into small wedges without instrument cheese-wiring and thus perform safer phacoemulsification while reducing the risk for posterior capsule rupture.

The role of the sewing ring in tissue healing: a pathologic study of explanted mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: Serious complications may occur after heart valve replacement, and many such patients will require reoperation. The study aim was to identify the pattern of tissue response around the sewing ring of those valves that have been explanted as a result of various valve-associated complications. METHODS: A total of 51 mechanical heart valves (MHVs) was explanted from 45 patients who had undergone reoperation for valve-related complications. The examination of the valves included an analysis of the operative findings, macroscopic findings, histopathology, and dissection of the sewing ring. RESULTS: The extent of tissue hyperplasia was variable around the sewing rings of valves explanted for various pathologies. In pannus, the hyperplastic tissue extended into the valve orifice and produced an obstruction to flow, whereas in thrombosed valves the thrombus was attached to the tissue at the annulus. In non-infective pathologies, the histology revealed cellular infiltration that was limited to the peripheral fabric layers of the sewing ring, though the extent of infiltration was not increased with the duration of implantation. In prosthetic valve endocarditis (PVE), the surrounding hyperplastic tissue was granulomatous, but cellular infiltration into the sewing ring was absent. The dissection of various models of explanted valves revealed that different types of filler and fixing mechanisms had increased the bulk of the sewing ring. CONCLUSION: Tissue hyperplasia of varying extent occurs around the sewing ring after MHV implantation. The cellular elements grow into the peripheral layers, but not the deeper layers, of the sewing ring. In PVE, there was an absence of cellular infiltration into the sewing ring.

Visual quality after posterior chamber phakic intraocular lens implantation in keratoconus.

PURPOSE: To quantify image-quality characteristics after correction of refractive error with a posterior chamber phakic intraocular lens (PC pIOL) in eyes with stable or stabilized keratoconus. SETTING: Narayana Nethralaya Postgraduate Institute of Ophthalmology, Bangalore, India. DESIGN: Case series. METHODS: Eyes with stable or stabilized keratoconus that had V4 Visian PC pIOL implantation for correction of refractive error were evaluated postoperatively for visual-quality metrics. RESULTS: Ten eyes of 7 patients had PC pIOL implantation. The preoperative mean refractive spherical equivalent of -7.21 diopters (D) ± 2.25 (SD) decreased to -0.55 ± 1.53 D at 6 weeks and -0.44 ± 1.21 D at 6 months. The efficacy index was 0.72 and the safety index, 1.13. The mean modulation transfer function (MTF) was 18.96 ± 14.16 (≥ 30 cycles per degree = good), the Strehl ratio was 0.11 ± 0.07 (1 = perfect), and the objective scatter index (OSI) was 4.45 ± 3.29 (≥ 1.5 = significant scatter). The MTF correlated inversely with secondary coma (P=.026), negative vertical coma (P=.014), and the root mean square (RMS) of total aberrations (P=.010) and higher-order aberrations (HOAs) (P=.015). The OSI was directly correlated with secondary coma (P=.021), secondary trefoil (P=.016), the RMS of total aberrations (P=.032), and HOAs (P=.050). CONCLUSION: In keratoconus, the refractive error could be corrected with the PC pIOL; however, the associated aberrations had an adverse impact on the ultimate visual quality and have to be addressed.

Understanding clinically undetected macular changes in early retinopathy of prematurity on spectral domain optical coherence tomography.

PURPOSE: To investigate macular changes in acute retinopathy of prematurity (ROP). METHODS: Fifty-four premature infants with ROP and 20 controls underwent routine ROP screening with indirect ophthalmoscopy and imaging. A tabletop spectral domain optical coherence tomography (SD-OCT) scanner (Spectralis; Heidelberg Engineering, Heidelberg, Germany) was converted into a handheld device to image infants in the office sans sedation. RESULTS: SD-OCT images were obtained in all infants in the office. On SD-OCT, 23 of 79 eyes (29.1%) with stage 2 ROP showed abnormal foveal changes despite clinically normal foveae. Of the 23 eyes, 2 distinct patterns of foveal involvement were observed: "pattern A," which was characterized by dome-shaped foveal elevation and cystoid spaces with highly reflective intervening vertical septae, and "pattern B," which was characterized by preservation of the foveal depression with fewer intraretinal cystoid spaces. These patterns were seen in 12 (52.2%) and 11 (47.8%) eyes, respectively. All eyes (100%) belonging to stage 1 ROP (27) and the normal group (40) had no abnormal SD-OCT changes. The mean central foveal thickness was 156.9 ± 28.3 µm, 206.5 ± 98.7 µm, and 135.9 ± 17.6 µm for stage 1, 2, and normal eyes, respectively (P < 0.001). Nineteen of the 23 eyes underwent serial imaging at 52 weeks' postmenstrual age (PMA), and all of them revealed normalization of foveal contours at this visit. CONCLUSIONS: SD-OCT changes of the macula in mild ROP have not been previously described. Our method reveals that infants may be imaged supine and unanesthetized in the office. We hypothesize that these transient foveal changes at the critical time of fovealization in premature infants may influence their visual acuity in the adult life.

Modified technique for epinucleus removal in posterior polar cataract.

The authors describe a novel technique for the removal of the sub-incisional epinucleus in cases of posterior polar cataracts. After the removal of the nucleus, the epinucleus is removed from the quadrant opposite to the section by aspiration using the phaco probe. Then hydrodissection is performed to dislodge the sub-incisional epinucleus, which is aspirated out. The rate of posterior capsular rupture decreased considerably with this technique because it reduced the manipulations required.

In vivo confocal microscopic findings of interlamellar stromal keratopathy induced by elevated intraocular pressure.

We report the confocal microscopic findings in a case of interlamellar stromal keratopathy induced by elevated intraocular pressure (IOP) after laser in situ keratomileusis (LASIK). In vivo confocal microscopy showed swollen and enlarged cellular structures and the presence of microlacunae separating the stromal collagen lamellae. Inflammatory mononuclear cells and granulocytes typically seen in patients with diffuse lamellar keratitis (DLK) were absent. Stopping the topical steroids with concurrent lowering of the IOP resulted in improvement in the uncorrected and best corrected visual acuities and was associated with resolution of the corneal findings. In vivo confocal microscopy is a useful tool to study interlamellar stromal keratopathy induced by elevated IOP after LASIK in humans and the response to treatment and to differentiate interlamellar stromal keratopathy from DLK.

Study on the gill of field crab, Paratelphusa hydrodromus (Herbst.) exposed to nickel.

Paratelphusa hydrodromus (Herbst.) was exposed to 50 ppm nickel chloride solution for a period of 10 days under laboratory conditions. The gills of the treated and non-treated animals were sectioned, stained and examined under a compound microscope and noticed significant changes such as enlargement of gill lamellae, lifting up and rupture of epithelial cells, enlargement of mid rachis, hyperplasia and hypertrophy, appearance of pyknotic nuclei and a general necrosis in the treated gills. Results suggest that a comparatively low concentration of nickel (50 ppm) is enough to elicit pathological changes in Paratelphusa hydrodromus.