Perceptions of undergraduate medical students regarding institutional online teaching-learning programme.

BACKGROUND: Medical education all over the country has been forced to shift to e-learning, mainly online classes. In this scenario, the medical education department (MEU) of a teaching hospital under a deemed university felt the need to study the satisfaction and usefulness of these classes, as perceived by the undergraduate medical students. METHODS: Questionnaire survey was planned. A specially designed questionnaire was created, keeping in mind, the study objectives. It was validated, and a pilot was conducted, for modifications and to calculate sample size. The questionnaire was administered by email as Google Forms. The responses, which included quantitative and qualitative responses, were analysed, and feedback points noted. Percentage level of satisfaction and usefulness was calculated with 95% confidence interval. To test the statistical significance of the association of satisfaction levels amongst students of different Phases, chi square test was used. RESULTS: On a scale scoring for satisfaction, 53.6% scored moderate, 31% high, and 15.4% low satisfaction. 49.8% of the students were less satisfied about attending classes from home; 15.7% felt it was better. 57.1% of the students found the concept of online learning moderately useful, 31.4% found it minimally useful, 11.5%, highly useful. CONCLUSIONS: The undergraduate medical students perceived moderate satisfaction and usefulness with the on-going online classes. They expressed the desire to resume routine physical classes, especially for practicals and clinics. Points of improvement of the online teaching-learning programme were also obtained. This study revealed sufficient feedback to be shared with all stakeholders, regarding improvements in the online classes.

Biallelic loss-of-function variants in TBC1D2B cause a neurodevelopmental disorder with seizures and gingival overgrowth.

The family of Tre2-Bub2-Cdc16 (TBC)-domain containing GTPase activating proteins (RABGAPs) is not only known as key regulatorof RAB GTPase activity but also has GAP-independent functions. Rab GTPases are implicated in membrane trafficking pathways, such as vesicular trafficking. We report biallelic loss-of-function variants in TBC1D2B, encoding a member of the TBC/RABGAP family with yet unknown function, as the underlying cause of cognitive impairment, seizures, and/or gingival overgrowth in three individuals from unrelated families. TBC1D2B messenger RNA amount was drastically reduced, and the protein was absent in fibroblasts of two patients. In immunofluorescence analysis, ectopically expressed TBC1D2B colocalized with vesicles positive for RAB5, a small GTPase orchestrating early endocytic vesicle trafficking. In two independent TBC1D2B CRISPR/Cas9 knockout HeLa cell lines that serve as cellular model of TBC1D2B deficiency, epidermal growth factor internalization was significantly reduced compared with the parental HeLa cell line suggesting a role of TBC1D2B in early endocytosis. Serum deprivation of TBC1D2B-deficient HeLa cell lines caused a decrease in cell viability and an increase in apoptosis. Our data reveal that loss of TBC1D2B causes a neurodevelopmental disorder with gingival overgrowth, possibly by deficits in vesicle trafficking and/or cell survival.

Efficacy, Safety and Immunogenicity of Sun's Ranibizumab Biosimilar in Neovascular Age-Related Macular Degeneration: A Phase 3, Double-Blind Comparative Study.

INTRODUCTION: The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun's ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). METHODS: This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun's ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). RESULTS: Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun's ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at -1% (-2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun's ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun's ranibizumab group and 14.6 letters in the reference ranibizumab group (p < 0.001 within both groups and p = 0.5275 between groups). The mean change in central macular thickness was comparable between groups (p = 0.7946). Anti-ranibizumab antibodies were found in one patient of the reference ranibizumab group, while neutralising antibodies were not found in any patients. Both products were well tolerated. CONCLUSION: Sun's ranibizumab biosimilar is found to be therapeutically equivalent to reference ranibizumab in patients with nAMD. There were no additional safety or immunogenicity concerns. TRIAL REGISTRATION: CTRI/2020/09/027629, registered on 07 September 2020.

Effect of dexamethasone implant on intraocular cytokines in diabetic macular edema.

Purpose: Our primary aim was to evaluate intraocular cytokines (IC) before and after dexamethasone in diabetic macular edema (DME). Our secondary aim was to study the early and late effects of single dexamethasone implant in DME. Methods: This before and after comparative study was conducted at the Department of Ophthalmology and Centre for Nanosciences at a quaternary referral center in Kerala, India, from September 2016 to September 2018. Patients underwent complete ophthalmological examination and cytokine analysis before and after dexamethasone implant. Levels of cytokines at baseline and repeat sample were studied. Results: Twenty-seven eyes (21 patients) were divided into two groups depending on time from baseline to second injection. Group 1 included patients with <3 months between the two samples - 12 (44.4%). Group 2 included patients with >3 months between the two samples -15 (55.6%). Best corrected visual acuity (BCVA) and central macular thickness (CMT) improved significantly post-dexamethasone in group 1, but not in group 2. Interleukin (IL)-4, IL-6, IL-10, vascular endothelial growth factor (VEGF), IL-1ß, interferon-gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), and IL-2 decreased post-injection in group 1. But cytokines increased post-dexamethasone in group 2, except IL-10. When compared to baseline, IL-6 reduced to half in group 1 (P-value 0.814) and it tripled in group 2 ( P-value 0.009). The level of VEGF in the first and second samples was not different in either group. Conclusion: Our study suggests that dexamethasone acts more on IC than VEGF in DME. This is significant in the first 3 months with a rebound effect on IL-6 after 3 months. Our study also suggests that repeat injection of DEX in DME should be done at 3 months to prevent deterioration of visual acuity (VA) and worsening of CMT.

Perceptions of faculty towards online teaching for undergraduate medical education: An interview-based qualitative study.

Background The Covid-19 pandemic drastically affected medical education. One consequence was the shift of teaching-learning process to the online mode. This left many teachers unprepared. Our medical education department of a large teaching hospital did a qualitative analysis of the perceptions of the faculty towards this forced change. Methods We conducted in-depth interviews with 10 of the nearly hundred undergraduate faculty of a teaching hospital in southern India, with a strength of 100 students per batch. The participants were chosen by purposive sampling so as to include all phases and seniority levels. Seven categories related to the topic of research were decided. These were given to the participants to then speak freely about. Standard methods for recording and transcribing were followed. Deductive content analysis was done to obtain the emergent themes. Results The faculty had a definite negative perception of online teaching. Lack of interaction, absence of immediate feedback and concerns about attendance were uniformly the biggest issues. Practical and clinical teaching was deemed nearly impossible to be taught online. The positives were the gradual comfort factor with online teaching, and the mental preparation for the long haul with this modality. Conclusion In-depth interview and its qualitative analysis proved useful in getting a deeper understanding of the perceptions of the medical faculty towards online teaching-learning. The negative and positive perceptions thus obtained have proved useful as feedback to the medical education department to suggest changes to improve the online teaching programme.

Relationship between diabetic retinopathy and diabetic peripheral neuropathy - Neurodegenerative and microvascular changes.

PURPOSE: To determine the relationship between diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and their associated risk factors. METHODS: We conducted a cross-sectional analysis on 500 patients who attended the Endocrinology department at a quaternary health care center in Kerala between November 2017 and April 2018. Patients above the age of 30 years with type 2 diabetes mellitus (DM) were included. They underwent a detailed medical history, dilated fundus examination for DR, assessment and grading of DPN, and blood investigations. Among these, 49 randomly selected patients without DR had peripapillary retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) assessed by optical coherence tomogram. RNFL and GCIPL changes in different grades of neuropathy were evaluated. RESULTS: Out of 500 patients, 303 (60.6%) were males and 197 (39.4%) were females. Prevalence of DR was 48% and DPN 71.8%. Risk factors for the development of DR included duration of DM >15 years, HbA1c (glycated hemoglobin) greater than 6.5%, serum creatinine more than 1.5 mg/dl, and the presence of DPN. There was a statistically significant association between DR and DPN. There was significant thinning of GCIPL in patients with moderate to severe neuropathy without DR. CONCLUSION: There is a significant association between DR and DPN and their severities. There are early changes in inner retinal layers of diabetic patients without microvascular changes of DR. These neurodegenerative changes parallel DPN in the course of DM. Our study stresses the importance of multidisciplinary approach in the management of diabetes and its complications.

Significance of monitoring vascular endothelial growth factor, monocyte chemoattractant protein-1 and Interleukin-8 in diabetic macular edema towards early identification of nonresponders to ranibizumab therapy.

Purpose: Identification of nonresponders prior to anti-vascular endothelial growth factor (anti-VEGF) therapy would help in the judicious clinical management of diabetic macular edema (DME) patients. Thus, a systematic study was initiated to identify nonresponding DME patient population undergoing ranibizumab treatment to figure out additional inflammatory components that may contribute to their nonresponsiveness to anti-VEGF therapy. Methods: A total of 40 patients recruited to this investigator-initiated trial received intravitreal ranibizumab monthly for 3 months. The fourth- and fifth-month injections were according to PRN protocol and the sixth-month injection was mandatory. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and VEGF in aqueous humor were measured for all the patients. Patients were grouped into responders/nonresponders on the formulated criteria and the levels of key pro-inflammatory cytokines were also measured between the two groups at baseline, 2 month and 5 months using cytometric bead array (CBA). Results: Eleven patients were categorized (29.72%) as responders and 10 patients (27.02%) as nonresponders. Nonresponders showed poorer BCVA (P = 0.024, 0.045, and 0.048 for 4, 5, and 6 months) and higher CMT (P = 0.021, 0.0008 and <0.0001 for baseline, 1, 2, 3, 4, 5, and 6 months) compared to responders. The cytokines IL-8, MCP-1 were significantly up regulated (P = 0.0048 and 0.029 for MCP-1 and IL-8) in nonresponders. Conclusion: Elevated MCP-1 and IL-8 levels found in the nonresponders could be used as a prognostic marker to identify these groups of patients and can help in developing alternative treatment options along with anti-VEGF therapy.

Pilot of a questionnaire study regarding perception of undergraduate medical students towards online classes: Process and perspectives.

BACKGROUND: The COVID-19 pandemic situation has forced a shift in medical education from physical classroom to virtual online teaching. However, students and teachers perceive this differently. It is important to study these perceptions to improve the teaching-learning process, and thus to validate the role of online learning in the country. OBJECTIVE: To document the process of a pilot for a questionnaire-based study regarding perception of undergraduate medical students towards on-going online classes. METHODS: Medical Education Department of a teaching hospital developed a new questionnaire with the primary objective of studying the satisfaction and usefulness of the online classes (e-Learning). Content validity was done. For the pilot work, 10% of the total student strength was targeted. Random purposive sampling from each phase of the undergraduate course was done to choose the participants. The questionnaire was administered via Google Classroom. It was an external, undeclared type of pilot. All the responses were documented and analysed for both changes in the questions as well as for statistical sample size derivation for the main study. RESULTS: Responses from 30 students were analysed for the pilot study. Based on the proportion of the level of satisfaction (23.3%) and usefulness (23.3%) of the on-going online classes observed, and with 20% relative precision and 95% confidence, the minimum sample size for the main study was calculated. The responses revealed the need for minor changes in the questionnaire tool for overall feasibility and achievement of the objectives of the main study. CONCLUSIONS: A pilot study is a necessary component for a research project, especially when it involves the use of a new tool. This paper shows the relevance of the same. The authors intend to convey the importance of documenting the processes of conduct of a pilot study, the issues involved therein, and the steps taken to resolve the same.

Lipoprotein Lipase Deficiency.

OBJECTIVES: To analyse the clinical and molecular spectrum of Lipoprotein Lipase (LPL) deficiency and to highlight the effect of a cost-effective indigenous diet for management of this disorder. METHODS: This is a single-centre retrospective study. Fifteen patients from 14 kindreds with severe hypertriglyceridemia (more than 1000 mg/dl) were evaluated for a period of 12.5 y at Amrita Institute of Medical Sciences, Kerala, India. RESULTS: Thirteen of 15 patients were referred after incidental detection of lipemic plasma, 1/15 had chylothorax in the neonatal period and 1/15 had pancreatitis. The mean age of presentation was 7 mo (ranging from 2 d to 4 y), and 20% of the patients had a positive history of consanguinity. Hepatomegaly (15/15), splenomegaly (9/15) and lipemia retinalis (14/15) were common findings. Lipemia retinalis was a useful non-invasive diagnostic tool. All the patients were subjected to diet modification and followed up at regular intervals. Fourteen of 15 complied with the diet, resulting in a dramatic improvement in the fasting lipid profile; only 1/15 developed pancreatitis. Genetic screening analysis was offered to 14/15 patients (1/15 was lost to follow-up); six different variants were identified, of which two were novel variants. CONCLUSIONS: Lipemic serum, chylothorax and recurrent pancreatitis in children should raise the suspicion of Lipoprotein Lipase deficiency. Early diagnosis and prompt initiation of a stringent fat-restricted diet are the keys to success for the management of LPL deficiency and prevention of pancreatitis.

Incidence and risk factors for intraocular pressure rise after transconjunctival vitrectomy.

Purpose: To study the incidence and risk factors of raised intraocular pressures (IOPs) in the follow-up of transconjunctival sutureless vitrectomy (TSV). Methods: A retrospective observational study was performed on 635 patients who underwent TSV under a single surgeon. The IOPs were recorded using a calibrated non-contact tonometer at seven postoperative visits, viz., day 1, 7 and 1, 3, 6 months, and 1 day and 1 month following silicone oil removal. Results: IOP rise was seen in 24.25% (154) out of the 635 eyes studied. Among patients under 50 years of age, 37.73% had an IOP rise, compared to 21.55% above 50 years (Odds Ratio 2.206). Among males, 30.32% had an IOP rise, as compared to 15.98% females (OR 2.287). In eyes with retinal detachment, 49.16% had raised IOP (OR 5.435), and 24.05% with proliferative diabetic retinopathy (OR 1.780), as opposed to 15.38% with macular hole and 12.32% with epiretinal membrane. This was statistically significant (P < 0.001). In eyes with silicone oil, 34.9% developed a rise in IOP (OR 2.738) as compared to 11.94% of other surgeries (OR 0.697). This was statistically significant (P < 0.001). Conclusion: We observed an increase in IOP postoperatively, more in those under 50 years, males and patients undergoing surgery for RD and PDR.

Clinical profile and outcome of endogenous endophthalmitis at a quaternary referral centre in south India.

Purpose: The purpose of this study is to evaluate the clinical profile, visual, anatomical and survival outcome of patients with endogenous endophthalmitis. Methods: Retrospective chart review of consecutive cases with endogenous endophthalmitis presenting from 2009-2016. Results: In our study, 41 eyes of 34 patients were included. Most common co-morbidity associated with endogenous endophthalmitis was Diabetes Mellitus (70.7%) and most common infective foci was UTI (73.2%). Among the culture positive cases, fungi and bacteria were evenly distributed, 76.93% were Gram positive bacteria and 23.07% were Gram negative. Fungal endogenous endophthalmitis was more commonly seen in immunosuppressed state (72.7%) and bilateral cases (66.7%). The mean presenting vision (log MAR) of patients who died during the study were poor compared to those who survived (P = 0.014) Poor mean visual acuity at presentation was associated with more death (P = 0.014). Eyes with poor presenting vision, fungal isolates, culture positivity and immune suppression had poor visual and survival outcome. Poor visual outcome was observed more frequently in eyes with Aspergillus infection (85.7%) compared to Candida (75%) and bacteria (58.3%). Evisceration was done for 5 out of 41 eyes (12.2%). Vitrectomy rate was 53.7% in our study, with 40% of them showing overall improvement in vision. Conclusion: Endogenous endophthalmitis is a sight threatening condition associated with high mortality particularly when caused by Aspergillus spp. in immunocompromised patients. Contrary to the prior published reports of endogenous endophthalmitis outside India, we found an equal distribution of fungal and bacterial organisms among our cases, with predominance of Aspergillus among fungal isolates and Gram-positive organism among bacteria. Fungal infections, especially with Aspergillus spp., resulted in poor visual and survival outcome.

Effect of intravitreal dexamethasone implant on the contralateral eye in recalcitrant radiation maculopathy.

Radiation maculopathy, a subset of significant radiation retinopathy, is one of the most common causes of visual loss following localized, regional, or whole-brain radiotherapy. Ozurdex (Allergan Inc., Irvine, CA, USA), a sustained-release intravitreal implant of 0.7 mg dexamethasone, has been used as an off-label treatment for treating recalcitrant radiation maculopathy. However, to the best of our knowledge, the beneficial effect of intravitreal dexamethasone in the contralateral eye in a patient with radiation maculopathy has not been described in the literature so far. In this case report, we report the efficacy of dexamethasone 0.7 mg intravitreal implant in recalcitrant radiation maculopathy which was refractory to intravitreal bevacizumab therapy. The patient showed good anatomical and functional outcomes in both the eyes after unilateral injection of intravitreal dexamethasone as evident by optical coherence tomography scans and fundus fluorescein angiography. It is noteworthy that the contralateral was not treated for 4 years. The case reveals systemic exposure of dexamethasone after intravitreal injection by demonstrating the bilateral effect after unilateral injection of intravitreal dexamethasone.

Does the clinical phenotype of mucolipidosis-IIIγ differ from its αß counterpart?: supporting facts in a cohort of 18 patients.

Mucolipidosis-IIIγ (ML-IIIγ) is a recessively inherited slowly progressive skeletal dysplasia caused by mutations in GNPTG. We report the genetic and clinical findings in the largest cohort with ML-IIIγ so far: 18 affected individuals from 12 families including 12 patients from India, five from Turkey, and one from the USA. With consanguinity confirmed in eight of 12 families, molecular characterization showed that all affected patients had homozygous pathogenic GNPTG genotypes, underscoring the rarity of the disorder. Unlike ML-IIIαß, which present with a broader spectrum of severity, the ML-III γ phenotype is milder, with onset in early school age, but nonetheless thus far considered phenotypically not differentiable from ML-IIIαß. Evaluation of this cohort has yielded phenotypic findings including hypertrophy of the forearms and restricted supination as clues for ML-IIIγ, facilitating an earlier correct choice of genotype screening. Early identification of this disorder may help in offering a timely intervention for the relief of carpal tunnel syndrome, monitoring and surgery for cardiac valve involvement, and evaluation of the need for joint replacement. As this condition may be confused with rheumatoid arthritis, confirmation of diagnosis will prevent inappropriate use of immunosuppressants and disease-modifying agents.

Ocular Manifestations of Pediatric Systemic Diseases.

Ocular manifestations that occur directly or indirectly as result of a pathologic process that involves other parts of the body, in a pediatric population, will be discussed here. While a myriad number of systemic conditions have ocular manifestations, its importance cannot be undermined because it has implications for both diagnosis and treatment. Often, the eye findings can give a clue to the systemic diagnosis and at other times, not managing the eye manifestations can lead to irreversible blindness although the systemic condition was treated well. So, it is important for all clinicians dealing with pediatric population to be aware of ocular manifestations of the common systemic conditions. The authors discuss the ocular manifestations of the following systemic conditions: Genetic and chromosomal anomalies, phakomatoses, metabolic disorders, infectious diseases, craniofacial anomalies, muscular disorders, inflammatory disorders and miscellaneous.

Genotype-phenotype analysis of von Hippel-Lindau syndrome in fifteen Indian families.

The general prevalence of the familial multi-organ tumor disorder, von Hippel-Lindau syndrome (VHL), was estimated to be 1 in 25-40,000 in western studies two decades back. Few studies were done in Indian sub-continent, amidst a surge in clinical reports on VHL specific manifestations. The syndrome is correlated with mutations of the gene VHL (located in Chr 3p25.3). We aimed to conduct a prospective case series describing phenotypic and genotypic characteristics in Indian population. The VHL-specific clinical and radiological features were collected from patients and family members. Genotypic changes such as deletion/duplication or point mutation in the VHL locus were identified using sequencing and MLPA. Thirty-one subjects, from fifteen families with diagnosed VHL, were included in the study. Multicystic pancreas was found in 71% (22/31), CNS hemangioblastoma in 68% (21/31), renal cell carcinoma and retinal angiomas in 23% (7/31) each, pheochromocytoma in 9.7% (3/31) of the population and endolymphatic sac tumor in one subject. Four families (9 subjects) had full length deletion of VHL, three families (4 subjects) had a deletion of exon 3, eight families (18 subjects) had different exonic, splice-site and intronic point mutations and one subject had a de novo in-frame indel in exon 1. Multicystic pancreas and CNS hemangioblastomas were the most common manifestations in our population. The phenotypic expression patterns in terms of tumorigenesis, tissue tropism and penetrance in comparison to the genotypic features were found to be different from previous correlative studies.

Intraocular gnathostomiasis: report of a case and review of literature.

Intraocular gnathostomiasis is a rare parasitic infection caused by the third-stage larvae of spiruroid nematode Gnanthostoma spp. seen mostly in tropical and subtropical regions. It is a food-borne zoonosis caused by ingestion of raw or undercooked freshwater fish, amphibians, reptiles, birds, and mammals, all of which are known to harbor advanced third-stage larvae of Gnanthostoma spp. To date, 74 cases of intraocular gnathostomiasis have been reported from 12 different countries. Only four countries have reported more than 10 cases each, and India shares the rare distinction of being one of them, with 14 cases. Surprisingly, not a single case of cutaneous gnanthostomiasis has ever been reported from India. We present one such case of intraocular gnathostomiasis in a 41-year-old male who presented with an actively motile worm attached to the iris, and we review the pertinent literature of all such cases reported from India.

Lipoprotein lipase deficiency in an infant.

Patients with isolated hypertriglyceridemia usually present with recurrent abdominal pain, pancreatitis, eruptive xanthomas, lipemia retinalis and hepatosplenomegaly. We describe the diagnosis and treatment of an infant with severe hypertriglyceridemia. The child was found to be heterozygous for two novel mutations in the lipoprotein lipase gene.