High-resolution HLA genotyping in inclusion body myositis refines 8.1 ancestral haplotype association to DRB1*03:01:01 and highlights pathogenic role of arginine-74 of DRß1 chain.

OBJECTIVES: Inclusion body myositis (IBM) is a progressive inflammatory-degenerative muscle disease of older individuals, with some patients producing anti-cytosolic 5'-nucleotidase 1A (NT5C1A, aka cN1A) antibodies. Human Leukocyte Antigens (HLA) is the highest genetic risk factor for developing IBM. In this study, we aimed to further define the contribution of HLA alleles to IBM and the production of anti-cN1A antibodies. METHODS: We HLA haplotyped a Western Australian cohort of 113 Caucasian IBM patients and 112 ethnically matched controls using Illumina next-generation sequencing. Allele frequency analysis and amino acid alignments were performed using the Genentech/MiDAS bioinformatics package. Allele frequencies were compared using Fisher's exact test. Age at onset analysis was performed using the ggstatsplot package. All analysis was carried out in RStudio version 1.4.1717. RESULTS: Our findings validated the independent association of HLA-DRB1*03:01:01 with IBM and attributed the risk to an arginine residue in position 74 within the DRß1 protein. Conversely, DRB4*01:01:01 and DQA1*01:02:01 were found to have protective effects; the carriers of DRB1*03:01:01 that did not possess these alleles had a fourteenfold increased risk of developing IBM over the general Caucasian population. Furthermore, patients with the abovementioned genotype developed symptoms on average five years earlier than patients without. We did not find any HLA associations with anti-cN1A antibody production. CONCLUSIONS: High-resolution HLA sequencing more precisely characterised the alleles associated with IBM and defined a haplotype linked to earlier disease onset. Identification of the critical amino acid residue by advanced biostatistical analysis of immunogenetics data offers mechanistic insights and future directions into uncovering IBM aetiopathogenesis.

Pregnancy outcomes in the medical management of glaucoma: An international multicenter descriptive survey.

PURPOSE: To determine if glaucoma medications are associated with pregnancy and/or postnatal complications. METHODS: Multicenter descriptive survey. Subjects were female patients 18-45 years who were previously pregnant with a diagnosis of glaucoma or ocular hypertension prior to pregnancy. Chart review queried diagnosis, glaucoma severity, and race. Survey questions were asked for each pregnancy and queried pregnancy age, medications used, and pregnancy outcomes/complications. RESULTS: 114 pregnancies of 56 patients (mean 2.0 pregnancies per patient) were included. Three pregnancies with therapeutic abortion were excluded from further analysis. Mean age during pregnancy was 29.1 ± 5.7 years. Of the 111 pregnancies, 20 (18.0%) used no medications and 91 (82.0%) used at least one medication. Medications were topical carbonic anhydrase inhibitors (n = 45), beta-blockers (n = 55), alpha-agonists (n = 56), and prostaglandin analogues (n = 28). Outcomes were: preterm contractions/labour (6.3%), miscarriage (4.5%), stillbirth (4.5%), induction of labour (11.9%), emergency/unplanned caesarean delivery (13.9%), neonatal intensive care unit (NICU) stay (15.8%), congenital anomalies (8.1%), and low birth weight (10.9%). Fisher exact test assessed outcome associations with individual agents, use of any agent, and different number of agents. Alpha-agonist use was associated with NICU stay: 25.5% rate (p = 0.012) in alpha-agonist use. Most of the alpha-agonist use NICU stays occurred in pregnancies with third trimester use. All other associations were not statistically significant. CONCLUSIONS: The data from this survey suggest an overall favourable safety profile for topical glaucoma medications in pregnancy, but further investigation is needed. Caution should be employed regarding third trimester alpha-agonist use owing to association with NICU stay.

Awareness and knowledge among paramedical staff about glaucoma surgeries and post-surgery counseling - A questionnaire based study at a tertiary eye care center in Central Rural India.

Purpose: To determine the level of awareness and knowledge about glaucoma surgery and post-surgery counseling amongst paramedical staff at a tertiary eye-care hospital. Methods: This observational cross-sectional study included a random sample of 94 hospital personnel: 37 general nurse midwives, 47 ophthalmic assistants, and 10 patient caretakers (PCTs). Participants were administered a questionnaire about glaucoma surgery and post-surgery counseling of patients. Results: The study included 41 (43.6%) females and 53 (56.4%) males. The mean age of the participants was 24.85 ± 4.54 years. All participants were aware of trabeculectomy surgery in glaucoma (100%). A total of 95.7% knew that surgery helps in controlling IOP, of whom 57 (60.6%) participants got information during their course of learning. Overall 53 (56.4%) believed that surgery is done when medication failure occurs, and 58 (61.7%) knew that surgery helps in preserving vision. A total of 63 (67.0%) participants knew to counsel patients to visit an ophthalmologist when called for and take the treatment as advised, whereas 74 (78.7%) correctly said to visit an ophthalmologist immediately if pain/diminution of vision/discharge occurs. Overall, PCTs were found to be having significantly better knowledge (P = 0.01) compared to others and they also reported ophthalmologists as the chief source of information. Conclusion: This study revealed that paramedical staff had an excellent awareness of trabeculectomy surgery. However, the knowledge and counseling parts of the questionnaire revealed less than satisfactory responses. So, there is a need to continuously educate paramedical staff members so that they can help in propagating information about the role of glaucoma surgery and the importance of proper follow-up.

Gonioscopic angle evaluation and its correlation with graft survival and post-operative ocular hypertension in patients of Descemet's stripping endothelial keratoplasty.

Purpose: To evaluate the gonioscopic changes in patients receiving Descemet's stripping endothelial keratoplasty (DSEK) without pre-existing ocular hypertension (OHT) and to report its correlation with post-surgery OHT, graft survival, and visual outcomes. Methods: Adult patients who underwent DSEK surgery from April 2014 to March 2018 with at least 2 years of follow-up were analyzed in this retrospective study. Demographic details, indication of DSEK, necessary anterior and posterior segment findings, and the post-DSEK OHT details were documented. Results: A total of 58 patients (23 males and 35 females) with a mean age of 61.44 ± 8.8 years were included in the study. The most common etiology for DSEK surgery was pseudophakic bullous keratopathy in 47 eyes (81.03%). A total of 22.41% (13/58) eyes showed elevated intra-ocular pressure (IOP) following DSEK surgery. The most common cause of IOP elevation was steroid-induced OHT in seven eyes (12.06%). Gonioscopy examination revealed areas of peripheral anterior synechiae (PAS) in 17 (29.3%) eyes. OHT was found in 4/17 (23.5%) eyes having PAS. Three of these cases required trabeculectomy + goniosynechiolysis (GSL), and the fourth case required GSL alone to control IOP. These four cases also required repeat DSEK for failed grafts. The mean pre-operative best corrected visual acuity was 1.62 logMAR (range 1.17-1.77), which gradually improved to 0.79 logMAR (range 0.3-1.77) after 2 years (p < 0.00001). Conclusion: PAS was found to be an important factor associated with post-DSEK ocular hypertension in our study. OHT in PAS cases required definitive surgical treatments to control IOP. It adversely affected the graft survival and in turn affected visual outcomes also.

Reasons for Delayed Presentation for Cataract Surgery in Patients of Lens Induced Glaucoma - A Questionnaire-based Study at a Tertiary Eye Care Centre of Central Rural India.

PURPOSE: To describe the socioeconomic profile, awareness level and reasons for the delay in accessing timely eye care for cataract surgery in patients of lens-induced glaucoma (LIG). METHODS: This cross-sectional observational study included all patients with LIG who presented to a tertiary eye care centre in central rural India between March 2019 to February 2020. Data were collected through a questionnaire. RESULTS: Out of the 731 patients included in the study, the majority were females (69.36%). The mean age of the patients at presentation was 62.66 ± 10.37 years. Only a few participants, 193 (26.40%) were aware of LIG. Lower socioeconomic profile, older age, female gender and illiteracy were found to be strongly associated with awareness about LIG (p < .001). Patients waiting for the winter season (58.27%) to get operated was the major reason for delayed presentation to the hospital. Other reasons for the delayed presentation were - need not felt (feeling that intervention was not necessary) due to good vision in other eye (14.36%), financial issues (11.63%), long travelling distance (7.11%), no caretaker (6.89%), medical illness (1.78%) and fear of surgery (0.55%). CONCLUSION: Delayed reporting for eye healthcare in patients of LIG is found to be multifactorial. Most patients preferred waiting for the winter season to get their eyes operated, which throws light on the mindset and ignorance of the patients in this part of central rural India. We further emphasize on strengthening the education and counseling efforts in the community to enable patients to access services in a timely fashion.

Bilateral laser peripheral iridotomy in a co-occurrence of unilateral iridocorneal endothelial syndrome and chronic angle closure glaucoma.

PURPOSE: To report a case of unilateral Iridocorneal endothelial (ICE) syndrome- Progressive iris atrophy (PIA) with an overlapping chronic angle closure glaucoma (CACG) and to highlight the effect of bilateral Laser peripheral iridotomy (LPI) in such a co-occurrence. CASE DESCRIPTION: A patient presented to us with bilateral gradual painless progressive diminution of vision. Both eyes (BE) had a clear cornea, shallow peripheral anterior chamber depth, grade 2 nuclear sclerosis, raised intraocular pressure and glaucomatous optic neuropathy. In addition, the Left eye (LE) had an irregular anterior chamber, peripheral anterior synechiae (PAS) extending to cornea, patchy iris atrophy, subtle corectopia and a low endothelial cell count on specular microscopy. Indentation gonioscopy led to the diagnoses of CACG BE with ICE syndrome- PIA LE. LPI was performed bilaterally. On Anterior Segment Optical Coherence Tomography (ASOCT), there was evident widening of the angle away from PAS in the Right eye as well as in the LE with PIA post LPI. CONCLUSION: This is a unique case of unilateral PIA with an associated CACG in BE. It is the first case demonstrating the effect of bilateral LPI in such a case scenario. Though not indicated in ICE syndrome, LPI did show short term evidence of significant widening of the angle away from areas of PAS even in the eye with PIA having a limited high PAS and a concurrent primary (chronic) angle closure disease.