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To examine ultrastructural changes in the trabecular meshwork (TM) in patients with primary and secondary glaucoma using scanning electron microscopy (SEM). This was a qualitative descriptive hospital-based study on the ultrastructure of the TM. Pure TM samples were collected after microincisional trabeculectomy from 26 patients with primary or secondary glaucoma and 10 control samples from eye bank donor corneas. SEM was used to analyze structural changes in the TM beams, corneoscleral meshwork (CSM), and juxtacanalicular (JCT) regions. Morphological features were compared between groups and correlated with histopathological findings. SEM revealed flattened and broadened TM beams in the JCT, resembling controls, often with a dumbbell configuration. Histopathological examination (HPE) and SEM showed rounded TM beams with considerable thinning, especially in primary angle-closure glaucoma (PACG), compared to primary open-angle (POAG) and pseudoexfoliation glaucoma (XFG). Maximum thinning in all primary glaucoma occurred in the CSM region, with minimal changes in the JCT region despite a reduction in cellularity in both regions. In steroid glaucoma, amorphous, glistening material was found on the TM beams in the JCT and CSM. XFG eyes displayed vesicular bodies adjacent to fibrillar material scattered diffusely over the TM beams, particularly in the CSM, differing from the platelet clumps seen in regular blood clots. TM beam thinning in primary glaucoma primarily affects the CSM region, sparing the JCT region. Amorphous deposits or vesicular bodies, seen only in steroid-induced glaucoma and XFG, suggest different mechanisms of TM damage in these glaucoma types. [ABSTRACT FROM AUTHOR]

Air-conduction (AC) and bone-conduction (BC) thresholds were measured to evaluate standard reference thresholds and recommend revisions to audiometer standards. AC and BC thresholds were measured from listeners with normal hearing (NH) and sensorineural hearing loss (SNHL) at three sites. NH participants (n = 53) were selected based on age (18–25 years old), normal AC thresholds, tympanometry, otoscopy, and absence of otologic disease. SNHL participants (n = 49) were selected based on AC thresholds, tympanometry, otoscopy, and absence of otologic disease. AC thresholds obtained from NH listeners averaged 3.7 dB hearing level (HL). Air-bone gaps (ABGs) occurred in NH and SNHL listeners above 2000 Hz and in SNHL listeners at 250 Hz. Corrections to standard reference equivalent threshold sound pressure levels are recommended. ABGs in listeners without conductive pathology result from incorrect reference threshold levels for frequencies above 2000 Hz. False ABGs increase with hearing-loss magnitude, probably the result of the effects of ambient and internal noise for low-level BC stimuli. False ABGs place patients at risk for unnecessary medical and surgical intervention. Reference threshold levels should achieve two objectives: (1) AC thresholds from young NH listeners should average 0 dB HL; and (2) ABGs from listeners with normal middle-ear function should average 0 dB. [ABSTRACT FROM AUTHOR]

The trabecular meshwork (TM) offers the maximum resistance to aqueous outflow that regulates the intraocular pressure. Newer ab interno procedures have opened up newer frontiers for understanding the functional relationship between the TM and Schlemm’s canal. This case provides newer anatomical insights from findings during intraoperative use of anterior segment optical coherence tomography during ab interno microincisional trabeculectomy. Growing evidence and intraoperative findings during ab interno trabeculectomy suggest that other parts of the TM and its intricate understanding of the physiology of the outflow pathway deserve more study. [ABSTRACT FROM AUTHOR]

Exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) represent a complex matrix of ocular age-related neurodegenerative changes. Numerous decades of research on this disease entity have highlighted the unique clinical features of ocular protein-complex aggregates, which lead to tissue dysfunction of the ocular outflow channels, leading to irreversible optic nerve damage and glaucoma. While genetic studies have reported several genes associated with XFS and XFG, numerous studies have shown their association with common systemic diseases such as ischemic heart disease, cerebrovascular accidents, and hypertension. Environmental factors are also reported to play a role in the disease pathogenesis by epigenetic control of gene expression and partly explain the difference in the prevalence rates of the disease process. Despite the identification of possible triggers for the disease onset or for the development of glaucoma, the exact mechanisms or the role of several reported risk factors in disease pathogenesis remain a mystery. This review comprehensively evaluated the several risk factors in XFS and XFG while discussing the interactive interplay between the risk factors that determine the disease onset or phenotype in XFS and XFG. [ABSTRACT FROM AUTHOR]

Purpose: Teaching and training of glaucoma fellows on the technique of Ahmed glaucoma valve (AGV) implantation surgery is very important. The purpose of this study was to describe the clinical outcomes and complications of AGV surgery performed by glaucoma fellows of a tertiary eye center from eastern India. Methods: This was a retrospective study based on electronic medical records. Thirty-five eyes operated with AGV by five glaucoma fellows from January 2016 to November 2020 were included. Best-corrected visual acuity, intraocular pressure (IOP), and number of antiglaucoma medications (AGMs) were the study outcome measures. Results: The mean (±standard deviation) age of the patients was 40.5 (±19.7) years. The follow-up period was 24.37 (±13.01) months. Both complete success (IOP <21 mmHg without additional AGM) and qualified success (IOP <21 mmHg with an additional AGM) were achieved in eight eyes each (22.8%). Failure of the surgery was noted in 19 eyes (54.3%) as there was a need for repeat surgery for IOP control in 12 eyes and a persistent IOP spike (IOP >21 mmHg with AGM beyond 3 months) in seven eyes. Despite a high rate of failure of the primary surgery, with the consultants' intervention, there was statistically significant improvement in vision and IOP in all patients (P < 0.01) at the last follow-up. Conclusion: AGV implantation is a challenging surgical skill to be acquired by the glaucoma fellows. [ABSTRACT FROM AUTHOR]

Exfoliation syndrome and exfoliation glaucoma comprise a unique age‑related ocular aggregopathy characterized by the accumulation of protein complex aggregates in different ocular structures. Recent literature and studies have expanded our knowledge of the clinical characteristic features, phenotypical variations, and molecular pathophysiology associated with disease onset or development of glaucoma. Despite years of studies on the various epidemiological, clinical, and molecular facets of the disease, the exact mechanism of disease onset, formation of aggregates, and the events that trigger the development of glaucoma marking irreversibility in the disease remains elusive. This review elaborates on the existing and new insights that we have gained over the years and highlights gaps in the knowledge about the disease that need future exploration. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate structural alterations and healing responses in the trabecular meshwork region with optical coherence tomography (AS-OCT) following after gonioscopy assisted transluminal trabeculotomy (GATT) and microincisional trabeculectomy (MIT). Methods: 73 eyes of 67 patients (M:F = 45:22) with ≥6 months of follow-up after MIT (n = 41) or GATT (n = 32) with or without combined cataract surgery were included for this prospective study. The angle as seen on AS-OCT at 1, 3, 6 months after surgery were evaluated for structural alterations like peripheral anterior synechiae (PAS), hyphema, and hyperreflective scarring responses. The scarring was graded according to the linear extent measured from the centre of the trabecular meshwork (TM) gutter to the sclera/cornea as mild (<250μ), moderate (250–500μ), and severe(˃500μ), while the pattern of scarring was graded as open saucer/gutter, closed gutter, and trench pattern. The association of the need for medication or surgical outcome and clinical variables and AS-OCT parameters including the pattern and severity of scarring were analysed using multivariate regression. Results: All eyes achieved significant reduction of IOP and number of medications with a final IOP of 15±3.2mm Hg at a mean follow-up of 8±32. months. While mild scarring was seen more common in MIT, severe scarring was seen in >65% of GATT eyes compared to 31% of MIT eye, p<0.001. An open saucer was equally seen in MIT and GATT while the trench pattern was more commonly seen in GATT eyes (>50%). Severe scarring in a trench pattern seemed to predict the need for medications for IOP control, though they independently did not seem to influence the final IOP or surgical outcome. Conclusion: A severe form of scarring in a trench pattern on AS-OCT predicted the need for glaucoma medications after MIGS surgery. Regular monitoring of the scarring responses by AS-OCT and clinical examination are necessary to identify those at need for medications after MIGS. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical efficacy of concurrent intravitreal bevacizumab (IVB) injection with trabeculectomy with mitomycin-C (MMC) in neovascular glaucoma (NVG). Methods: Patients with NVG who underwent trabeculectomy with concurrent IVB (group 1) and those who underwent IVB sequentially, followed by trabeculectomy with MMC (group 2) in 1–2 weeks between January 2021 and August 2022, were included in this retrospective hospital-based study. The need for medications for intraocular pressure (IOP) control at 6 months in the two groups was the primary outcome measured and compared between the groups. The association of the need for medications postoperatively with clinical variables was assessed using stepwise multivariate regression statistics. Results: We finally included 40 patients (n = 12 in group 1, n = 28 in group 2) with no significant differences in presenting age between groups. The IOP at 1 day and 1 week were not significantly different between groups though the IOP at 1, 3, and 6 months. IOP was lower in group 1 eyes with the 6-month IOP, being significantly lower in group 1, P = 0.05. Three eyes in group 1 and 11 eyes in group 2 required anti-glaucoma medications in the postoperative period. Multivariate regression identified preoperative IVB >3 (β =0.7, P < 0.001) and recurrent vitreous hemorrhage (β = 0.7, P = 0.004) as prognostic factors (R2 = 40.6%) determining the need for anti-glaucoma medication (AGM) postoperatively in both groups. Conclusion: Concurrent IVB with trabeculectomy with mitomycin-C is a feasible alternative in patients with NVG with refractory high-presenting IOP. This may serve to address raised IOP as well as retinal ischemia, thereby improving surgical success rates in the most challenging NVG cases. [ABSTRACT FROM AUTHOR]

Purpose: To report the histopathologic correlates of trabecular meshwork (TM) specimens procured by microincisional trabeculectomy (MIT) for different severities of glaucoma (early glaucoma: visual field mean deviation [MD] <−6 dB, moderate glaucoma: MD from − 6 to − 12 dB, and advanced glaucoma: MD <−12 dB). Methods: TM specimens from four patients undergoing MIT with or without cataract surgery were analyzed by routine histopathology for structural changes. The number of cells, the number of cells with spindle-shaped nuclei suggestive of epithelial–mesenchymal transformation (EMT), and the distance between the trabecular beams were calculated using different tools on freely available ImageJ software using the line or pint/count tool. Results: The TM specimens procured from two early and two advanced glaucoma cases showed decreasing cellularity and decreased compact arrangement of the trabecular beams in severe disease stages. The number of cells and preserved architecture in all four specimens were evident, with > 50 cells being present per section in all four cases despite the glaucoma being of advanced disease stage in two patients. Conclusion: The TM specimens obtained from MIT can be utilized for downstream analysis using different molecular methods for studying the molecular events in the tissue from early to severe glaucoma. [ABSTRACT FROM AUTHOR]

Individuals with hearing loss are at risk for cognitive decline. The traditional approach to audiological care does not typically involve a team approach that addresses cognitive concerns. While cognitive screening is within the scope of practice in audiology, audiologists are not typically trained in interpreting screening results or providing rehabilitation that supports cognitive health. However, as growing evidence shows that hearing loss is tied to cognitive decline, a team approach is required to support whole-person care. Speech–language pathologists, who specialize in optimizing communication, are best situated to collaborate with audiologists to provide holistic aural rehabilitation. Audiologists and speech–language pathologists who partner to support a client's communication skills and social relationships play an important role in the life of an individual with hearing loss. In this perspective, we describe relevant background information about hearing loss and cognition and present an interprofessional approach to aural rehabilitation for adults with hearing loss who have cognitive concerns. We also discuss implications for future research. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape across many solid organ malignancies and form part of routine clinical practice in many tumours. As indications for monotherapy, doublet therapy and combination approaches with chemotherapy and targeted agents expand, clinicians must be aware of the wide range of possible immune-related adverse events (irAEs). Common toxicities, including rash, colitis, hepatitis and pneumonitis are well described in the literature, and have established diagnostic and management algorithms. Rarer toxicities, often with an incidence of less than 1%, are less defined. These syndromes can be poorly recognised, may take on a fulminant course and do not have established or evidence-based diagnostic and management strategies. As such, patients may experience increased morbidity, mortality and poorer outcomes, related both to these irAEs as well as how the treatment of these may affect the management of their underlying malignancy. In this review, we aim to explore the incidence, potential biomarkers, pathogenesis, diagnostic work-up and clinical sequelae of a selection of uncommon irAEs, with a focus on myocarditis, neurological and haematologic syndromes. Further prospective research is required to accurately define the incidence and pathogenesis of these conditions, with the aim of increasing clinician awareness of rare irAEs and to assist with a more personalised and mechanism-based approach to these syndromes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical applicability of intraoperative predictors for surgical outcomes after gonioscopy-assisted transluminal trabeculotomy (GATT) and microincisional trabeculectomy (MIT). Methods: Consecutive patients with primary, or secondary glaucoma (trauma, aphakic, or status post-retinal surgeries) with uncontrolled IOP>21mm Hg, who were scheduled to undergo GATT or MIT with or without significant cataract surgery, at a tertiary eye centre in East India between September 2021 to March 2023, were included. All surgeries were done by a single surgeon. Blanching and Trypan blue (0.4%) staining after intracameral injection using a 25 canula, were analysed in each video. The extent/pattern of blanching and blue staining in each eye was analysed objectively using an overlay of a circle with 12 sectors and a protractor tool to quantify the degrees or quadrants of blanching/staining. Multivariate regression was used to identify predictors for surgical success or the need for medications after surgery. Result: Of 167 eyes that were included (male: female- 134: 33), 49 eyes and 118 eyes underwent GATT and MIT, respectively, with 81 of 167 eyes undergoing concurrent cataract surgery. All eyes had a significant reduction in the number of medications after surgery. Blanching was seen in 154 of 167 eyes in a mean of 2±1.8 quadrants with 41% of eyes showing a blanching effect in >3 quadrants. Of 99 of 167 eyes where Trypan blue staining was assessed, staining in a venular, diffuse haze, or reticular pattern of staining was seen in 73 eyes, 26 eyes showed blue staining in >2 quadrants, with 16% staining in >3 quadrants. Surgical success was not predicted by the quadrants of blanching, blue staining, or other clinical variables (age, visual field, baseline intraocular pressure, type of surgery). The variables significantly predicting the need for medications included blanch (r = -0.1, p = 0.03), and blue staining (r = -0.1, p = 0.04) in <2 quadrants. Conclusions: Blanching and Trypan blue staining in >2 quadrants after GATT or MIT can serve as surrogate predictors for the need for medications. However more studies are mandated to find predictors for surgical success after GATT or MIT. [ABSTRACT FROM AUTHOR]

Introduction: Newer inhalational agents, like sevoflurane and desflurane, offer advantages of rapid induction and early recovery due to their low blood gas solubility. However, cost remains a major drawback of these agents, despite the reduction in agent consumption achieved through low flow anaesthesia. Aim: To evaluate the recovery profile and cost-effectiveness of sevoflurane and desflurane using low flow anaesthesia in adults. Materials and Methods: A randomised clinical study was conducted at, Department of Anaesthesia, Bharati Vidyapeeth Medical College, Pune, Maharashtra, India, during October 2019 to August 2021, with 60 patients classified as American Society of Anaesthesiologists (ASA) I or II, aged 18-65 years, undergoing elective surgeries lasting 1-4 hours under general anaesthesia with the low flow technique. Group S received sevoflurane, while group D received desflurane. Anaesthesia was maintained using a 50/50 mixture of oxygen/air and either sevoflurane or desflurane, depending on the group. The inhalational agents were titrated intraoperatively to achieve a Minimum Alveolar Concentration (MAC) of approximately one. The amount of inhalational agent consumed was calculated, and recovery profiles were studied. The means of continuous variables were compared using an Independent sample t-test, with p-values <0.05 considered significant. Results: In Groups S and D, the mean ages were 39.17 years and 41.5 years, and the percentages of males were 30% and 50%, respectively. The mean times to swallowing, spontaneous eye opening, limb movements, establishing spontaneous regular breathing, responding to verbal commands, extubation, stating a name on command, and achieving a modified Aldrete score =9 in minutes were 6.13, 4.87, 5.07, 4.57, 7.40, 8.97, 10.40, and 11.50, respectively. These values were significantly lower in group D. The mean cost per hour and average volume consumption were significantly higher in group D. Conclusion: The study concludes that desflurane provides faster and better recovery from anaesthesia. Although the total cost of desflurane was higher compared to sevoflurane, its use can be beneficial for faster emergence, early transfer from the Post Anaesthesia Care Unit (PACU), and earlier discharge from the hospital. [ABSTRACT FROM AUTHOR]

Purpose: To compare visual field progression in severity-matched pseudoexfoliation glaucoma (XFG) and primary glaucoma after intraocular pressure (IOP) reduction by filtering surgery.Methods: Patients with XFG (n=32), primary open-angle glaucoma (POAG, n=33) or primary angle closure glaucoma (PACG, n=28) that underwent routine cataract and glaucoma filtering surgery by the same surgeon (APR) between May 2017 and September 2021, were included for this prospective study. Rate of progression (ROP) was determined using guided progression analysis and compared between XFG and primary glaucoma. Multivariate regression was done to analyse the factors responsible for progression in each group.Results: Visual field progression after surgery was noted in 48 eyes (n=11 XFG, 18 POAG and 19 PACG eyes) at a mean follow-up of 10± 5.6 months after surgery with RVI seen in 18 of 48 eyes. The final IOP (p=0.8) and mean ROP (p=0.09) were not significantly different between XFG and primary glaucoma. The XFG eyes had a greater number of eyes (36%) showing an ROP worse than − 5dB/yr, with 45% of eyes showing an IOP spike > 5mm Hg, and a higher mean IOP spike between visits. The ROP in eyes with RVO and > 5mm Hg IOP spikes was greater in XFG than in POAG or PACG. In the multivariate analysis, higher IOP fluctuations > 5mm Hg, and associated retinal vein occlusions (RVO) were significant factors for visual progression greater than − 5dB/year (R2=53.5%) in POAG and XFG eyes. Age, gender, baseline MD, and number of medications before surgery or at final follow-up did not influence visual progression rates in either group.Conclusion: A higher IOP fluctuation > 5mm Hg and associated RVO were the significant factors predicting visual field progression after filtering surgery in XFG and POAG eyes. Control of both IOP-dependent and -independent mechanisms of VF progression is therefore essential in these eyes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the short-term clinical outcomes of microincisional trabeculectomy (MIT), a new technique of ab-interno trabeculectomy. Methods: Consecutive patients with open-angle glaucoma identified from the hospital database that underwent MIT with or without cataract surgery between September 2021 to June 2022 at a tertiary eye centre in East India, were screened. Those with a follow-up of < 6 months or with incomplete data were excluded. MIT was done ab-interno using microscissors and microforceps in 2–4 clock hours of the nasal angle via a temporal incision. The intraocular pressure (IOP) reduction at 6 months, and reduction in the number of medications after surgery were analysed. Surgical success (IOP>6 and <22 mm Hg), complications, angle features on anterior segment optical coherence tomography (ASOCT), and the need for additional surgeries were analysed. Results: We included thirty-two eyes of 32 patients with open-angle glaucoma (including n = 9 eyes that underwent concurrent cataract surgery) with a preoperative mean IOP of 22 ±11.1 mm Hg and visual field index of 47±37.9%. All eyes achieved >30% IOP reduction, with a final IOP of 14±6.9 mm Hg at 6 months. Surgical success in 31 of 32 eyes with complete success seen in 28 eyes with none of the eyes requiring >1 medication for IOP control. Hyphema was seen in 4 eyes, while transient IOP spikes at 1 day-1 month were seen in 5 eyes, none of which required any additional interventions. One eye with persistent raised IOP at 1 month required incisional trabeculectomy for uncontrolled IOP with 2 medications. Conclusion: MIT, a new technique of ab-interno trabeculectomy, is effective in terms of IOP control and reduction in the number of medications while having fewer complications. Long-term studies comparing the efficacy of MIT with incisional trabeculectomy, or other procedures are warranted in the future. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcomes of operating on "complex cataracts" by the glaucoma fellows. Patients and Methods: This was a retrospective study done at a tertiary referral eye care centre in eastern India. After obtaining IRB approval, a retrospective chart review of all patients who underwent "complex" cataract surgery by one of four long-term (2 years) glaucoma fellows between January 2016 and November 2020 was conducted. 'Complex' was defined as cataracts complicated with pseudoexfoliation syndrome, phacodonesis with or without blunt ocular trauma, posterior polar cataract, small pupil, co-existent corneal opacity or uveal coloboma, post-glaucoma filtering surgery, post-vitreoretinal surgery, co-existent glaucoma or post-laser iridotomy and monocular patients. Results: Out of a total of 677 eyes done by the glaucoma fellows during the study period, 83 eyes had complex cataract surgery and completed the six-week post-operative follow-up. Intraoperative surgical complications like posterior capsular rent or vitreous loss were noted in 36 of the cases. Thirty of the eyes were left aphakic. Despite a high rate of complications, the LogMAR best-corrected visual acuity (mean ± standard deviation) improved from the preoperative level of 1.7 (± 0.5) to 1.0 (± 0.8) at post-operative six weeks, significant at p < 0.001. As far as the surgeon's experience was concerned—less than or more than a year since joining the fellowship—there was statistically no difference in the final visual acuity. The group with greater experience had shorter surgical time and lesser complications though this difference was not statistically significant. Conclusion: This is the first study in the literature reporting the outcomes of "complex" cataract surgery performed by glaucoma fellows. Though high rates of postoperative complications were noted in this study, the mean best-corrected visual acuity improved significantly in all eyes after the surgery. [ABSTRACT FROM AUTHOR]

"Myanmar in Crisis: Living with the Pandemic and the Coup" is a book that provides rare insight and analysis of the chaos in post-coup Myanmar. The book covers a range of topics, including the motivations behind the Civil Disobedience Movement, the economic repercussions of the coup, and the role of China in Myanmar. It also explores the mindset of the Tatmadaw (Myanmar's military) and the potential future of the country. The book suggests that Myanmar is now embroiled in a revolutionary struggle and faces a long period of low-intensity conflict. International support for Myanmar is limited, and the country may have to find change from within. [Extracted from the article]

A method for testing auditory processing of non-linguistic speech-like stimuli was developed and evaluated. Monosyllabic words were temporally reversed and distorted. Stimuli were matched for spectrum and level. Listeners discriminated between distorted and undistorted stimuli. Three groups were tested. The Normal group was comprised of 12 normal-hearing participants. The Senior group was comprised of 12 seniors. The Hearing Loss group was comprised of 12 participants with thresholds of at least 35 dB HL at one or more frequencies. The Senior group scored lower than the Normal group, and the Hearing Loss group scored lower than the Senior group. Scores for forward compressed speech were slightly higher than backward compressed speech but the difference was not statistically significant. Retest scores were slightly higher than scores on the first test, but the difference was not statistically significant. Large differences in discrimination of distorted speech were observed among the three groups. Age and hearing loss separately affected performance. The depressed performance of the Senior group may be a result of "hidden hearing loss" that is attributed to cochlear synaptopathy. The backward-distorted speech task may be a useful non-linguistic test of speech processing that is language independent. [ABSTRACT FROM AUTHOR]

Purpose: Pseudoexfoliation glaucoma (XFG) is often associated with a higher rate of intraoperative complications and failure. This study aims to compare the long-term clinical and surgical outcomes of cataract surgery alone versus combined surgery in XFG. This was a retrospective comparative case series. Methods: All patients with XFG who underwent either cataract surgery alone [group 1: either phacoemulsification, PHACO/small-incision cataract surgery (SICS), n = 35] or combined surgery (group 2: phacotrabeculectomy, PHACOT or SICS + trabeculectomy, n = 46) from 2013 to 2018 by a single trained surgeon were screened and recalled for a detailed clinical examination, including Humphrey visual field analysis at 3-monthly intervals for a minimum of 3 years. Surgical success (intraocular pressure, IOP, <21 mm Hg and >6 mm Hg with (qualified success) or without medicines, complete success, survival rates, visual field changes, and need for additional procedures/medicines for IOP control were compared between groups. Results: A total of 81 eyes of 68 patients with XFG were included in this study (groups 1–35 eyes and groups 2–46 eyes each). Both groups achieved 27–40% IOP reduction from preoperative IOP levels, P < 0.001. Surgical success rates were similar in both groups (complete success 66% vs 55%, P = 0.4), qualified success 17% vs 24%, P = 0.8, in groups 1 and 2). Kaplan–Meier analysis showed a marginally better survival rate for group 1, 75% (55–87%), than group 2, 66% (50–78%), at 3 and 5 years which was not significantly different. The number of eyes that progressed at 5 years after surgery (5–6%) was similar in both groups. Conclusion: Cataract surgery can be as effective as combined surgery in XFG eyes with regards to final visual acuity, long-term IOP profile, and visual field progression, and complications/survival rates are comparable between the two procedures. [ABSTRACT FROM AUTHOR]

Purpose: The past few years have been difficult in the lives of most glaucoma patients in view of the COVID-19 pandemic. Our aim was to find out patients' perspective and disruption of their quality of life during the COVID-19 pandemic by conducting a telephone survey among glaucoma patients. Methods: This was a cross-sectional study involving the glaucoma patients of a tertiary eye care hospital in India. Patients who had completed at least five years of follow-up before 2020 were randomized by a random number generator. A validated (forward–backward translation and completed pilot analysis) set of 14 questionnaires was administered to the patients, the latter of whom were telephonically interviewed by one of the investigators in February 2022. The entire data was audio-recorded. Statistical Package for the Social Sciences (SPSS) version 26 was used. Results: Out of 1141 patients with >5 years of follow-up, 103 were selected by randomization. A large group of 46 patients (44.6%) admitted to glaucoma affecting their daily activities. Only 12 (11.6%) admitted to being irregular with their drops. Thirty-four (33%) patients felt that their glaucoma was deteriorating and 31 (30.1%) had fear of blindness. Ninety-five patients (92.7%) felt that they were safe under the care of the treating doctor. There were 46 (44.6%) out of 103 patients who did not turn up for follow-up for six months or more. Lockdown (36.2%) and travel-expenses (27.6%) were the two most common reasons for the loss to follow-up visits. Conclusion: Nearly half of the long-term glaucoma patients were lost to follow-up during the COVID-19 pandemic. Glaucoma affecting daily lives and fear of losing vision turned out to be significant observations in the telephone survey. This fear seemed to be ameliorated by the majority still feeling safe by being in touch with their doctor for continued care even during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Glaucoma is the largest cause of irreversible blindness with a multifactorial genetic etiology. This study explores novel genes and gene networks in familial forms of primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) to identify rare mutations with high penetrance. Thirty-one samples from nine MYOC-negative families (five POAG and four PACG) underwent whole-exome sequencing and analysis. A set of prioritized genes and variations were screened in an independent validation cohort of 1536 samples and the whole-exome data from 20 sporadic patients. The expression profiles of the candidate genes were analyzed in 17 publicly available expression datasets from ocular tissues and single cells. Rare, deleterious SNVs in AQP5, SRFBP1, CDH6 and FOXM1 from POAG families and in ACACB, RGL3 and LAMA2 from PACG families were found exclusively in glaucoma cases. AQP5, SRFBP1 and CDH6 also revealed significant altered expression in glaucoma in expression datasets. Single-cell expression analysis revealed enrichment of identified candidate genes in retinal ganglion cells and corneal epithelial cells in POAG; whereas for PACG families, retinal ganglion cells and Schwalbe's Line showed enriched expression. Through an unbiased exome-wide search followed by validation, we identified novel candidate genes for familial cases of POAG and PACG. The SRFBP1 gene found in a POAG family is located within the GLC1M locus on Chr5q. Pathway analysis of candidate genes revealed enrichment of extracellular matrix organization in both POAG and PACG. [ABSTRACT FROM AUTHOR]

Purpose: To report the early postoperative causes of intraocular pressure (IOP) spikes after complete circumferential gonioscopy-assisted transluminal trabeculotomy (GATT) using anterior segment optical coherence tomography (ASOCT). Methods: This was retrospective interventional case series of patients who underwent circumferential GATT by a single surgeon (APR) from 2021 to 2022 at a tertiary eye care in East India and who developed IOP spikes at 1 day-2 weeks (immediate) or early (> 2 weeks– 2 months) after GATT. The intraocular pressure (IOP), glaucoma medications, and angle evaluation by ASOCT at 1 week, and 1 month were compared between the two groups. Results: Thirty-two eyes of 32 consecutive patients, aged 40± 20.1 years (20 exfoliation glaucoma, 9 juvenile open-angle, and 3 developmental glaucoma), that developed IOP spikes between immediate (n=20) or early (n=12) IOP spikes after GATT, were included. Immediate postoperative spikes were seen in 20 eyes due to retained viscoelastic (n=8), hyphema (n=8) in uncontrolled hypertension, and peripheral anterior synechiae (PAS) (n=6) of which only one eye required medication at 2 months. Causes of immediate IOP spikes on ASOCT included an inverted/reattached trabecular shelf, iris strands in eyes with abnormal iris in developmental glaucoma, and PAS in 1– 2 quadrants. Causes of early IOP spikes included PAS > 3 quadrants (n=8), and hyperreflective fibrotic tissue over TM (n=4) with 50% requiring medications at 2 months. The ASOCT features predicting the need for medications were PAS > 3 quadrants (OR=8.4[2.2– 14.3], p=0.03) and fibrotic TM closure (OR=5.4, [3.6– 10.2], p=0.003). One eye with macrohyphema 3 days after surgery owing to uncontrolled hypertension (owing to the stoppage of medicines), required additional incisional trabeculectomy within 1 month of surgery. Conclusion: Immediate IOP spikes are mostly self-resolving as opposed to early IOP spikes > 2 weeks that require medications after GATT. Gonioscopic PAS > 3 quadrants, and fibrotic TM closure were the main identifiable ASOCT causes predicting the need for medications after GATT. [ABSTRACT FROM AUTHOR]

Vitreoretinal surgeries either in the form of external compression by buckles or by increasing the intraocular volume by tamponades can cause a significant rise in intraocular pressure (IOP), causing glaucoma to be one of the most common consequences of vitreoretinal surgeries despite improved surgical techniques. Identifying the mechanism that causes the raised IOP is crucial as the management of glaucoma can differ accordingly. Intravitreal (IVT) injections in the form of IVT steroids or anti-vascular endothelial growth factor (anti-VEGF) injections can also cause a significant rise in the IOP and effect, especially the glaucomatous eyes, which are already predisposed. Not just the overlapping clinical features make the diagnosis confusing but also associated scarring of the conjunctiva, and the presence of episcleral hardware in some cases due to scleral buckle make the surgical management of glaucoma in these eyes very challenging. In this review, we describe in detail the various mechanisms causing secondary glaucoma post vitreoretinal surgeries with a focus on how to distinguish between them. We also discuss the possible consequences of anti-VEGF agents on IOP, various surgical challenges, and modifications with newer surgical options in the management of this refractory glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To compare the glaucoma assessment skills among general ophthalmologists in their referral patients over 5 years.Methods: This was a retrospective auditing of the electronic medical record database. Details of consecutive new glaucoma patients seen in the glaucoma services of a tertiary eye care institute in 2013 and 2018 were collected. Details of each patient included the clinical presentation, baseline intra-ocular pressure (IOP), type and severity of glaucoma, referral details, gonioscopy, HVF (Humphrey visual field) data, and the number of medications. Statistical tests used were the Chi-square test and T test using SPSS version 22.Results: Of 28,886 medical records screened, 211 and 568 new glaucoma patients were retrieved in 2013 and 2018, respectively. The patients presenting in 2018 were younger (58.1 ± 15.4 years) at presentation than in 2013 (65.6 ± 15.2 years), P < 0.01, and also had higher baseline IOP (IOP ≥40 mm Hg was found in 9.5% in 2018 versus 2.4% in 2013; P < 0.01). The percentage of eyes with presenting visual acuity worse than 20/400 or 20/600 was higher in the patients presenting in 2018 (22.2% vs. 15.1%; P = 0.03). Although primary glaucoma predominated in both periods, the number of eyes referred to as disc suspects showed an increase in 2018 (4.7% to 14.4%; P < 0.01). Among 195 and 517 referrals in 2013 and 2018, respectively, the documentation of clinical findings were dismally poor in both the groups in terms of absent gonioscopy (99% vs. 98.2%, P = 0.4), absent disc details (89.6% vs. 91%, P = 0.5), or absent visual field analysis (79.1% vs. 74.8%, P = 0.2). However, the missing IOP values were significantly better in the latter year (77.3% vs. 57.2%; P < 0.01).Conclusion: The increase in the number of new glaucoma patients and referrals did not show a corresponding improvement in documentation of findings except for IOP recording among general ophthalmologists. Hence, we need to re-emphasize the training of general ophthalmologists on basic glaucoma evaluation to improve their referral ability. [ABSTRACT FROM AUTHOR]

Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Resistance mechanisms mainly involve secondary mutations in the KIT receptor tyrosine kinase gene indicating continued dependency on the KIT signaling pathway. The fact that the type of secondary mutation confers either sensitivity or resistance towards TKIs and the notion that secondary mutations exhibit intra- and intertumoral heterogeneity complicates the optimal choice of treatment in the imatinib-resistant setting. Therefore, new strategies that target KIT independently of its underlying mutations are urgently needed. Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthesis and is FDA-approved for the treatment of chronic myeloid leukemia (CML) that is resistant to at least two TKIs. HHT has also shown activity in KIT-mutant mastocytosis models, which are intrinsically resistant to imatinib and most other TKIs. We hypothesized that HHT could be effective in GIST through downregulation of KIT expression and subsequent decrease of KIT activation and downstream signaling. Testing several GIST cell line models, HHT led to a significant reduction in nascent protein synthesis and was highly effective in the nanomolar range in IM-sensitive and IM-resistant GIST cell lines. HHT treatment resulted in a rapid and complete abolishment of KIT expression and activation, while KIT mRNA levels were minimally affected. The response to HHT involved induction of apoptosis as well as cell cycle arrest. The antitumor activity of HHT was confirmed in a GIST xenograft model. Taken together, inhibition of protein biosynthesis is a promising strategy to overcome TKI resistance in GIST. [ABSTRACT FROM AUTHOR]

Mammalian embryogenesis requires rapid growth and proper metabolic regulation1. Midgestation features increasing oxygen and nutrient availability concomitant with fetal organ development2,3. Understanding how metabolism supports development requires approaches to observe metabolism directly in model organisms in utero. Here we used isotope tracing and metabolomics to identify evolving metabolic programmes in the placenta and embryo during midgestation in mice. These tissues differ metabolically throughout midgestation, but we pinpointed gestational days (GD) 10.5–11.5 as a transition period for both placenta and embryo. Isotope tracing revealed differences in carbohydrate metabolism between the tissues and rapid glucose-dependent purine synthesis, especially in the embryo. Glucose’s contribution to the tricarboxylic acid (TCA) cycle rises throughout midgestation in the embryo but not in the placenta. By GD12.5, compartmentalized metabolic programmes are apparent within the embryo, including different nutrient contributions to the TCA cycle in different organs. To contextualize developmental anomalies associated with Mendelian metabolic defects, we analysed mice deficient in LIPT1, the enzyme that activates 2-ketoacid dehydrogenases related to the TCA cycle4,5. LIPT1 deficiency suppresses TCA cycle metabolism during the GD10.5–GD11.5 transition, perturbs brain, heart and erythrocyte development and leads to embryonic demise by GD11.5. These data document individualized metabolic programmes in developing organs in utero.Metabolomics analysis of the mouse embryo shows a metabolic shift towards the tricarboxylic acid cycle between gestational days 10.5 and 11.5, leading to the subsequent development of organ-specific metabolic programmes. [ABSTRACT FROM AUTHOR]

Glaucoma represents one of the most important ocular diseases causing irreversible ganglion cell death. It is one of the most common causes of visual impairment and morbidity in the elderly population. There are various tests for measuring visual function in glaucoma. While visual field remains the undisputed method for screening, diagnosis, and monitoring disease progression, other tests have been studied for their utility in glaucoma practice. This review discusses some of the commonly used tests of visual function that can be routinely used in clinics for glaucoma management. Among the various modalities of testing visual function in glaucoma, this review highlights the tests that are most clinically relevant. [ABSTRACT FROM AUTHOR]

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selectively controls their transport and translation during adaptation to BRAF-targeted therapy. UHMK1 inactivation induces cell death by disrupting therapy induced metabolic reprogramming, and importantly, delays resistance to BRAF and MEK combination therapy in multiple in vivo models. We propose selective mRNA processing and translation by UHMK1 constitutes a mechanism of non-genetic resistance to targeted therapy in melanoma by controlling metabolic plasticity induced by therapy. Different adaptive mechanisms have been reported to reduce the efficacy of mutant BRAF inhibition in melanoma. Here, the authors show BRAF inhibition induces the translational regulation of metabolic genes leading to acquired therapy resistance. [ABSTRACT FROM AUTHOR]

Purpose: To report unusual associations, atypical clinical presentations, and outcomes of tailored treatment of viral uveitis and glaucoma.Methods: Patients diagnosed with viral uveitis with associated glaucoma, seen at a tertiary eye care center between 2013 and 2020, were screened. Twenty-four patients with unclassified or atypical clinical presentations of viral uveitis, atypical clinical course, or with diagnostic challenges and associated glaucoma, were included. Patients with classical features of viral anterior or posterior uveitis, other forms of autoimmune/infectious/traumatic uveitis, were excluded.Results: Viral re-activation causing recurrent choroidals after glaucoma filtering surgery responsive to systemic antiviral therapy, massive pigment dusting/plume as a presenting feature, multiple progressive focal anterior synechiae similar to iridocorneoendothelial (ICE) syndrome, were seen in this cohort of unusual viral uveitis in glaucoma. A high index of suspicion helped diagnose a viral etiology in cases with high intraocular pressure (IOP) after uneventful Ahmed glaucoma valve surgery (AGV) or post-YAG capsulotomy laser, presumed Posner-Schlossman syndrome with multiple recurrences or presumed steroid glaucoma. All patients responded well with anti-viral and tailored concomitant steroids, anti-glaucoma therapy with loss of visual acuity seen in one eye developing optic atrophy.Conclusions: Uncommon clinical presentations or associations of viral uveitis in glaucoma should be kept in mind. A high index of suspicion and tailored prompt treatment may ensure good outcomes preventing further visual morbidity in glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To report the clinical profile and visual impairment in various stages of neovascular glaucoma (NVG) at a tertiary eye center in East India.Methods: The electronic medical records of the hospital database of patients with neovascular glaucoma seen between 2013 and 2020 were reviewed. Gonioscopic details were used to stratify patients into nonspecified NVG (Group 1), open-angle NVG (Group 2), and closed-angle NVG (Group 3). The clinical profile, angle features, cause of NVG, systemic associations, visual impairment, and blindness (defined as logarithm of the minimum angle of resolution, LogMar >1.3 at baseline and at final follow-up), and outcomes of medical/surgical interventions were compared between the three groups.Results: Of 846 eyes of 810 patients with NVG (Group 1, n = 564 eyes, Group 2, n = 61 eyes, and Group 3, n = 220 eyes), at baseline, the blindness rates in Groups 3 and 2 were 90 and 75%, respectively. The time from a previous intervention to the onset of NVG ranged from 3 to 5 months, while the median duration of NVG was about 4-4.5 months (0.03-120 months). Multivariate regression identified a longer duration of NVG as the only variable associated with poor final visual acuity.Conclusion: Visual morbidity by NVG remains as high as 75-90% in developing countries, even with the availability of anti-VEGFs and after improved management/investigative at all stages. [ABSTRACT FROM AUTHOR]

Anterior megalophthalmos usually presents early in life with megalocornea, deep anterior chamber, raised intraocular pressure, glaucomatous optic nerve damage and iridodonesis/stromal thinning with positive family history. We report atypical features and presentations in two patients (four eyes) with nonfamilial megalophthalmos. While the first patient, a male, presented at 51 years of age with megalocornea, cataract, phacodonesis, normal pupillary dilatation/ normal iris and advanced glaucoma, the second patient presented with iridodonesis with stromal thinning, aphakia and advanced glaucoma. The family history was negative in both patients. The vitreous index was unusually high, >70% in all four eyes, owing to aphakia in the second patient and possible late presentation/ variant phenotype in the first patient. Thus, atypical features such as greater vitreous length, absent iris involvement and late-onset adult presentation are common in non-familial anterior megalophthalmos. Clinical surprises due to varied phenotypes should be kept in mind in such cases. [ABSTRACT FROM AUTHOR]

Purpose: The key differences in cell death mechanisms in the trabecular meshwork (TM) in adult moderate and severe primary glaucoma remain still unanswered. This study explored key differences in cell death mechanisms in the trabecular meshwork (TM) in adult moderate and severe primary glaucoma. Design: In-vitro laboratory study on surgical specimens and primary cell lines. Methods: Select cell death-related proteins differentially expressed on mass spectrometric analysis in ex-vivo dissected TM specimens patients with severe adult primary open-angle (POAG) or angle-closure glaucoma (PACG) compared to controls (cadaver donor cornea) were validated for temporal changes in cell death-related gene expression on in-vitro primary human TM cell culture after 48 hours (moderate) or 72 hours (severe) oxidative stress with H2O2 (400– 1000 uM concentration). These were compared with histone modifications after oxidative stress in human TM (HTM) culture and peripheral blood of patients with moderate and severe glaucoma. Results: Autophagy-related proteins seemed to be the predominant cell-death mechanism over apoptosis in ex-vivo dissected TM specimens in severe glaucoma. Analyzing HTM cell gene expression at 48 hours and 72 hours of oxidative stress, autophagy genes were up-regulated at 48– 72 hours of exposure in contrast to apoptosis-related genes, showing down-regulation at 72 hours. There was associated increased expression of H3K14ac in HTM after 72 hours of oxidative stress and in peripheral blood of severe POAG and PACG. Conclusion: A preference of autophagy over apoptosis may underlie stage transition from moderate to severe glaucoma in the trabecular meshwork or peripheral blood, which may be tightly regulated by epigenetic modulators. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate differences in the iris and angle parameters in psuedoexfoliation syndrome (PXF) and pseudoexfoliation glaucoma (PXG) using anterior segment optical coherence tomography (ASOCT).Methods: Patients with PXF or PXG were compared using ASOCT with primary open-angle glaucoma POAG eyes as controls in this noninterventional comparative study conducted at a tertiary eye care center in East India. All angle parameters, TM length, and iris thickness were analyzed from the enhanced depth imaging (EDI) single scans obtained. Quadrant scans were used for the calculation of iris volume using a custom-built in-house software. In particular, the software performs multiple operations including edge detection, connected components, and thresholding to localize and segment the iris. Differences in the iris volume/thickness and TM length in PXF and PXG with POAG were analyzed.Results: A total of 225 eyes were included, which included 75 PXG and 98 PXF cases and 52 POAG with a mean age of 67 ± 9.7 years at presentation. The algorithm repeatability and reproducibility was also established with correlation coefficients more than 99% which was substantiated with Bland-Altman plots. The iris volume (calculated in 197 images of 225 eyes) did not differ significantly in PXF and PXG eyes, although both had significantly greater volume compared to POAG eyes. The iris volume or other angle parameters including TM length did not correlate with clinical variables such as IOP, age, or visual field indices.Conclusion: Iris parameters or TM length do not explain pathogenesis of glaucoma in pseudoexfoliation. [ABSTRACT FROM AUTHOR]

Purpose: Pseudoexfoliation (PXF) is a unique form of glaucoma characterized by accumulation of exfoliative material in the eyes. Changes in tear profile in disease stages may give us insights into molecular mechanisms involved in causing glaucoma in the eye. Methods: All patients were categorized into three main categories; pseudoexfoliation (PXF), pseudoexfoliation glaucoma (PXG) and cataract, which served as control. Cytokines, transforming growth factor β1 (TGFβ1), matrix metalloproteases (MMPs) and fibronectin (FN1) were assessed with multiplex bead assay, enzyme-linked immunosorbent assay (ELISA), gelatin zymography, and immunohistochemistry (IHC) respectively in different ocular tissues such as tears, tenon's capsule, aqueous humor (AH) and serum samples of patients with PXF stages. Results: We found that TGFβ1, MMP-9 and FN1 protein expression were upregulated in tears, tenon's capsule and AH samples in PXG compared to PXF, though the MMP-9 protein activity was downregulated in PXG compared with control or PXF. We have also found that in PXG tears sample the fold change of TGF-α (Transforming Growth Factor-α), MDC (Macrophage Derived Chemokine), IL-8 (Interleukin-8), VEGF (Vascular Endothelial Growth Factor) were significantly downregulated and the levels of GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), IP-10 (Interferon- γ produced protein-10) were significant upregulated. While in AH; IL-6 (Interleukin-6), IL-8, VEGF, IFN-a2 (Interferon- α2), GRO (Growth regulated alpha protein) levels were found lower and IL1a (Interleukin-1α) level was higher in PXG compared to PXF. And in serum; IFN-a2, Eotaxin, GM-CSF, Fractalkine, IL-10 (Interleukin-10), IL1Ra (Interleukin-1 receptor antagonist), IL-7 (Interleukin-7), IL-8, MIP1β (Macrophage Inflammatory Protein-1β), MCP-1 (Monocyte Chemoattractant Protein-1) levels were significantly upregulated and PDGF-AA (Platelet Derived Growth Factor-AA) level was downregulated in the patients with PXG compared to PXF. Conclusions: Altered expression of these molecules in tears may therefore be used as a signal for onset of glaucoma or for identifying eyes at risk of developing glaucoma in PXF. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate changes in central corneal thickness (CCT) following vitrectomy. Methods: All consecutive old and new patients referred to glaucoma services for possible secondary glaucoma after vitrectomy and who had undergone corneal pachymetry between July 2013 to June 2020, were included. The eye that developed elevated intraocular pressure (IOP) and was diagnosed clinically as glaucoma after vitrectomy, was labelled as the "affected" eye. The contralateral eye of the patient with normal IOP and no history of vitrectomy was labelled as the "control" eye. The difference in CCT in the affected eye and the contralateral control eye (ΔCCT) and CCT were compared between different age groups. Correlation of CCT in the affected eye with age, diagnosis, type of surgery done, lens status and pre-existing glaucoma was done using multivariate regression analysis. Results: Of 127 eyes of 120 patients (M:F = 85:35), the average CCT in the affected eye was significantly higher than the unaffected contralateral control eye (p<0.0001). The ΔCCT in eyes presenting at an age <25 years was higher (median 582, 497–840) than those that presented later (median 518, 384–755), p <0.0001, with maximum ΔCCT seen in eyes that had undergone vitrectomy at age<12 years. The CCT in the affected eye was significantly higher in aphakic eyes (588±81.6 microns) than in pseudophakic eyes (552±79.03 microns), p = 0.03. On multivariate analysis, age<25 years remained as a significant influencer of CCT in the affected eye (β = -1.7, p<0.001, R2 = 28.3%). Conclusions: Young age group<25 years are more prone to corneal remodelling and CCT changes after vitrectomy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the microRNA (miRNA) profile in patients with different stages of pseudoexfoliation (PXF). Methods: Peripheral blood of patients with PXF (naïve to medical therapy and with no systemic disease/drugs) with ocular hypertension (OHT) and pseudoexfoliation glaucoma (PXG) was evaluated in triplicate for miRNA profiling using polymerase chain reaction (PCR) arrays. Those identified in the discovery stage were validated with evaluation of serum transforming growth factor-β 1 (TGF-β 1) levels by ELISA. The downstream targets of TGF-β 1 and unfolded protein response (UPR) were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Predicted targets of the identified miRNA and KEGG pathway analysis were done using miRbase and DIANA tools mirPathv3.1. Results: We found hsa-miR-122-5p, hsa-miR-124-3p and hsa-miR-424-5p to be upregulated in PXG targeting 3 specific pathways namely TGF-β 1, fibrosis/ECM and proteoglycan metabolism with common effectors like SMAD/3/2. The unfolded protein response (UPR) genes were significantly downregulated in all stages of PXF suggesting this as the key mechanism for protein aggregates in PXF syndrome. Serum TGF-β 1 was significantly upregulated as disease progressed to later stages in PXG. This elevation in advanced stages was associated with significantly differential expression of downstream pathways and fibrotic genes in OHT compared to PXG predominantly through the SMAD3, a canonical pathway marker. Conclusion: Circulatory miRNA differentially regulating TGF-β 1 and downstream targets including UPR genes may be the key mechanisms for glaucoma onset in PXF. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate efficacy and outcomes of manual small incision cataract surgery with trabeculectomy (Group 1) and phacoemulsification with trabeculectomy (Group 2) in pseudoexfoliation glaucoma (PXG).Methods: In this retrospective comparative observational case series, All patients with PXG who underwent either small incision cataract surgery or phacoemulsification with trabeculectomy from 2011-2015 were studied. Data compared included best corrected visual acuity (BCVA), intraocular pressure (IOP), total surgical time, and incidence of intra/postoperative complications.Results: A total of 82 (Group 1) and 64 (Group 2) subjects were included for the study. The baseline IOP and anti-glaucoma medications in both groups were comparable pre-operatively (group 1 = 26 ± 10.3 mmHg, group 2 = 23 ± 13.9 mmHg, P = 0.1). The IOP at final follow up between the two groups was not statistically significant (group 1 = 12 ± 3.2 mmHg, group 2 = 14 ± 1.8 mmHg, P = 0.2).The average total time of surgery (group 1 = 40 ± 21.6 min, group 2 = 34 ± 14.8 min, P = 0.4) was not statistical significant between groups. The incidence of post-operative complications were similar in both groups (P = 0.95).Conclusion: Manual small incision cataract surgery with trabeculectomy is noninferior in PXG patients with comparable surgical outcomes, when compared with phacoemulsification with trabeculectomy. [ABSTRACT FROM AUTHOR]

Exosomes, small-sized extracellular vesicles, carry components of the purinergic pathway. The production by cells of exosomes carrying this pathway remains poorly understood. Here, we asked whether type 1, 2A, or 2B adenosine receptors (A1Rs, A2ARs, and A2BRs, respectively) expressed by producer cells are involved in regulating exosome production. Preglomerular vascular smooth muscle cells (PGVSMCs) were isolated from wildtype, A1R−/−, A2AR−/−, and A2BR−/− rats, and exosome production was quantified under normal or metabolic stress conditions. Exosome production was also measured in various cancer cells treated with pharmacologic agonists/antagonists of A1Rs, A2ARs, and A2BRs in the presence or absence of metabolic stress or cisplatin. Functional activity of exosomes was determined in Jurkat cell apoptosis assays. In PGVSMCs, A1R and A2AR constrained exosome production under normal conditions (p = 0.0297; p = 0.0409, respectively), and A1R, A2AR, and A2BR constrained exosome production under metabolic stress conditions. Exosome production from cancer cells was reduced (p = 0.0028) by the selective A2AR agonist CGS 21680. These exosomes induced higher levels of Jurkat apoptosis than exosomes from untreated cells or cells treated with A1R and A2BR agonists (p = 0.0474). The selective A2AR antagonist SCH 442416 stimulated exosome production under metabolic stress or cisplatin treatment, whereas the selective A2BR antagonist MRS 1754 reduced exosome production. Our findings indicate that A2ARs suppress exosome release in all cell types examined, whereas effects of A1Rs and A2BRs are dependent on cell type and conditions. Pharmacologic targeting of cancer with A2AR antagonists may inadvertently increase exosome production from tumor cells. [ABSTRACT FROM AUTHOR]

Aim: To compare the outcomes of Ahmed glaucoma valve (AGV) pediatric FP8 versus the large-sized adult FP7 implants in an adult secondary glaucoma. Methods: Patients who underwent AGV implantation from January 2011 to December 2016 for adult secondary glaucoma (due to causes other than post-vitreoretinal/buckle surgery glaucoma) with a follow-up of 6 months were included for this retrospective study. Success was defined as IOP > 6 mm Hg and < 21 mm Hg without any loss of vision, with or without the need of anti-glaucoma medications or additional procedures for control of IOP. Hypertensive phase was defined as IOP > 21 mmHg at any visit in the first 6 months of postoperative follow-up period, while failure was defined as IOP > 21 mm Hg even after medications or additional procedures, need of removal of implant or loss of light perception. Cumulative survival rates and intraoperative or postoperative complications along with IOP profiles were compared between the implants. Results: Of 43 patients, 19 patients underwent FP7 and 24 patients underwent FP8 Ahmed Glaucoma valve implantation. The IOP significantly reduced in both groups from baseline (31 ± 8.2 mm Hg in FP7 eyes and 37 ± 13.1 mm Hg in FP8 eyes) by a mean of 64 ± 23.5% in FP8 and 64 ± 21.5% in FP7 group, respectively, p = 0.8 with comparable final IOP of 16.5 mm Hg and 16.9 mm Hg, respectively, p = 0.9. Both groups had 75% qualified success rates at 20 months after surgery with similar rates of need for postoperative medications or incidence of hypertensive phase. The FP8 eyes had more frequent conjunctiva-related complications in eyes with prior surgeries and preoperative conjunctival scarring while the other complications were similar in the two groups. Conclusion: Surgical outcomes of adult FP7 and pediatric FP8 AGV in adult secondary glaucoma seem to achieve similar IOP control and success rates. This suggests that smaller-sized FP8 can be used in adult glaucoma with good surgical outcomes albeit with careful case selection in eyes with extensive preoperative scarring to avoid conjunctival thinning-related complications postoperatively. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the disease burden of pseudoexfoliation (PXF) disease stages from East and South India. Design: Prospective hospital based study of patients seen at 4 tertiary centres. Subjects, participants, and/or controls: Consecutive old and new patients of pseudoexfoliation with normal intraocular pressure (IOP), raised IOP (PXF with Ocular hypertension, OHT) and irreversible disc/field changes (pseudoexfoliation glaucoma, PXG) seen from April 2016-March 2017 at a tertiary centre in Odisha, East India and 3 centres in Andhra Pradesh and Telangana, South India, recruited into the prospective study were screened for baseline characteristics. Methods: The clinical and demographic details including visual acuity, laterality, intraocular pressure (IOP) with details of medical/surgical therapy at presentation were collected from the hospital database at all 4 centres. Intervention or exposure: The World Health Organization WHO visual criteria were used for defining visual impairment/absolute blindness in different disease stages. Outcome measures: The visual impairment/blindness rates with comorbidities in the anterior/posterior segment in PXF, OHT and PXG at baseline were compared and the influence of age, IOP fluctuations and laterality was analysed using multivariate logistic regression. Results: Of 6284 PXF eyes (of 3142 patients) included from all centres, OHT and PXG was seen in 2.1% and 29% respectively which included 3676 (>50%) bilateral PXF eyes. Reversible visual impairment rates caused by PXF associated co-morbidities in PXF and OHT were 33% and 26% respectively with cataract being the major cause (67% in PXF and 74% in OHT). Irreversible blindness rate was higher in bilateral PXG eyes (30.5%) compared to bilateral PXF (23.2%) or bilateral OHT (21.6%) with overall absolute blindness rates of 28.2% at presentation. Older age (p<0.001), bilaterality and higher baseline IOP were significantly associated with higher rates of blindness in PXF eyes. Conclusion and relevance: Pseudoexfoliation is associated with ≥30% visual impairment across all stages and 28% absolute blindness rate which is a huge hidden burden of glaucoma. Adequate disease staging and assessment of comorbidities is required for accurate prognostication at baseline and reducing avoidable pseudoexfoliation blindness. [ABSTRACT FROM AUTHOR]

Purpose: To study the perceptions, attitude, knowledge of the disease, and impediments to seeking early eye care in caregivers of children with childhood glaucoma.Methods: The study included new and old children diagnosed with childhood glaucoma (which included congenital glaucoma and developmental glaucoma) at a tertiary hospital of east India. The caregivers were administered a video-based questionnaire through open-ended questions intended to collect demographic and other personal details such as caregiver's socioeconomic status, knowledge, attitude towards eye health, and other social barriers. The responses were analyzed using thematic analysis technique into different buckets such as social status, knowledge/attitude, and sociocultural beliefs while individual responses in each bucket were analyzed.Results: Of a total of 43 patients included,> 75% of patients came from places> 200 km from the eye care centre with> 50% coming from> 300 km. Most patients presented either <1 year (42%, n = 18) or> 3 years (52%, n = 22) with only 2% (n = 3) presenting between 1-3 years of age. The mother was the first person of contact to diagnose the eye abnormality in> 45% of patients. Comparing differences among children who presented within 1 year of first diagnosis and those that presented later, caregivers hailing from long-distance> 200 km from an eye care center, monthly income <5000 INR, and those with social/cultural taboos (like children's eyes should not be operated) were more likely to seek delayed eye care for congenital glaucoma, P < 0.001.Conclusion: Impediments in seeking early eye care for blinding diseases in children (including distance from the nearest hospital, low socioeconomic constraints, and sociocultural beliefs/taboos) mandate serious policies towards improving education about eye disease and eye health among caregivers. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose is to evaluate the results of the modified direct phaco-chop technique of cataract surgery in eyes with pseudoexfoliation. METHODS: All patients with pseudoexfoliation and visually significant cataract with normal intraocular pressure (IOP) and optic nerve that underwent cataract surgery by the same surgeon using Infiniti®, OZil® Torsional handpiece (Alcon Labs), were included for this retrospective hospital-based study. Direct vertical or horizontal chop technique was used in all cases with parameters set as required for quadrant removal with high vacuum after the initial cleanup of cortex under the capsulorhexis. To allow better visualization of the hardness of the nucleus core, the sides of the lens were scooped out a central well with vacuum with maximum chopping done centrally within the rhexis as the first step to enable better assessment of the depth of burying the chopper for direct chop. Intraoperative details recorded and analyzed included ultrasound time and cumulative dissipated energy. The mean visual acuity and IOP before and after surgery were recorded at 1 day, 1 week, and 1 month. Complications during or after surgery were noted. RESULTS: A total of 138 patients with a mean age of 62 ± 6.7 years underwent phachop technique of phacoemulsification for nuclear cataract grades of nuclear sclerosis 2–4 with significant improvement in visual acuity from baseline (0.26) to 3 months (0.82), P < 0.001. The mean ultrasound torsional amplitude and cumulative dissipated energy (CDE) were greater for brown cataract of grading >3, P = 0.02. A total of 8 patients had intraoperative zonular dialysis in 1 quadrant (none in >1 quadrant), which was not associated with intraoperative vitreous prolapse in 6 eyes. CONCLUSIONS: Direct modified phaco-chop technique may be a safe technique in pseudoexfoliation due to minimal zonular stress with successful outcomes and reduced complications. [ABSTRACT FROM AUTHOR]