The intersection of ophthalmology and neurology: Diagnosing acute strokes through visual symptoms.

PURPOSE: To document how acute cerebrovascular accidents (CVAs) present first to an ophthalmologist. METHODS: Retrospective, observational, unicentric hospital-based study. The electronic medical records of new patients who presented to the Neuro-ophthalmology department of a tertiary eye hospital in the month of August 2022 were reviewed. Those with symptoms suggestive of an acute stroke requiring urgent neuroimaging were chosen for further study. RESULTS: Out of the 710 new patients, 31 had a known CVA and presented with field defects (4.3%). We recognized nine new patients, subsequently diagnosed to have a CVA, initially presenting with ocular symptoms such as homonymous hemianopia in seven cases and two others as transient obscuration of vision and internuclear ophthalmoplegia. CONCLUSION: Posterior circulation strokes commonly present first to an ophthalmologist, the early recognition of which is of utmost importance.

Long-term effect of increasing water intake on repeated self-assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease.

Background: The aim of this study was to determine the long-term effect of increasing water intake in patients with autosomal dominant polycystic kidney disease (ADPKD) on longitudinal changes in health-related quality of life (HRQoL) in the setting of a clinical trial. Methods: Self-completed HRQoL (using the KDQoL-SF, v.1.3 questionnaire) was assessed annually in participants of a 3-year randomized controlled clinical trial (n = 187), allocated (1:1) either to increase water intake to reduce urine osmolality to ≤270 mosmol/kg (implemented by dietetic coaching, self-monitoring tools, text messaging) or continue usual water intake. Results: Overall, 96% and 81.8% of participants (n = 187) completed the questionnaire at the baseline and final study visits, respectively. At baseline, the physical component summary score (PCS) and mental component summary score (MCS) were similar in the two groups (P > 0.05) and the five dimensions with the lowest scores in both groups were: energy and fatigue; general and overall health; sleep; emotional well-being; and pain. Within each group, there were no longitudinal changes over time. At the final visit, the PCS was higher in the increased water intake group (51.3 ± 7.6, mean ± standard deviation) compared to the usual water intake group 48.8 ± 9.3; P = 0.037) whereas the MCS was numerically similar. The improvement in the PCS was due to higher sub-scale values for physical functioning and pain (both P < 0.05). By multivariate analysis, only baseline PCS and height-corrected total kidney volume were associated with the final PCS (P < 0.05). Conclusion: HRQoL scores remained stable over a 3 year period, and were not adversely affected by the intervention to increase water intake. Future studies should evaluate the clinical significance of the higher PCS in the increased water intake group.

A Rare Case of Familial Methemoglobinemia with Congenital Heart Disease.

Methemoglobinemia is a rare dyshemoglobin disorder which can either be congenital or acquired. Dyshemoglobin disorders can be asymptomatic or symptomatic. We narrate the case of a 12-year-old girl who presented with a fever, cough, and oxygen saturation of 85%. She was diagnosed with COVID-19, along with a large atrial septal defect and pulmonary arterial hypertension. Arterial blood gas analysis revealed normal partial pressure of oxygen and on 100% exposure to oxygen, blood color turned chocolate brown. After the resolution of COVID-19 in 10 days, the patient was treated with oral ascorbic acid and successful atrial septal defect repair. It is important to suspect dyshemoglobin disorder in a patient who presents with hypoxia/hypoxemia.

Lethal mycotic pseudoaneurysm presenting as isolated sixth nerve palsy.

Pseudoaneurysm of the internal carotid artery caused by skull base osteomyelitis (SBO) is a lethal condition seen in immunocompromised patients, predominantly those with diabetes mellitus. Cranial nerve involvement is a common complication and generally indicates a poor prognosis. We report the case of a 62-year-old diabetic patient who presented with isolated sixth cranial nerve palsy. She had uncontrolled blood sugar levels and high erythrocyte sedimentation rate, and she suffered from pyelonephritis. Neuroimaging detected SBO with multiple secondary mycotic pseudoaneurysms prominent at the petrocavernous junction. Ischemia is the most common etiology for an isolated abducens nerve palsy, but in certain cases neuroimaging is warranted to prevent life-threatening complications. This case highlights the importance and urgency of identifying and managing such conditions.

Mixed cryoglobulinaemia vasculitis secondary to marginal zone lymphoma in a patient with end-stage renal failure on haemodialysis.

Cryoglobulinaemia vasculitis can present with a variety of symptoms and there is limited data on the incidence and presentation of cryoglobulinaemia vasculitis in haemodialysis patients. We report a case of a 63-year-old male who had a series of presentations with rash, visual changes, abdominal pain, weight loss, fevers and digital ischaemia. This is on a background of a congenital single kidney with end-stage renal failure secondary to diabetes and hypertension, receiving haemodialysis for nearly 5 years. He initially experienced a leukocytoclastic vasculitis rash confirmed on skin biopsy, followed by multiple hospital presentations for undifferentiated abdominal pain and fever of unknown source. Jejunal biopsy revealed intestinal vasculitis. His peripheral blood flow cytometry and bone marrow biopsy were consistent with marginal zone lymphoma (indolent subtype, IgM kappa clone). Further testing revealed a type II cryoglobulinaemia consisting of an IgM kappa monoclonal band with polyclonal IgG (cryocrit 5%). A diagnosis of cryoglobulinaemia vasculitis was established and he was treated with pulsed methylprednisolone and rituximab therapy. However, after receiving three doses of rituximab the patient developed a presumed vasculitis-associated pulmonary haemorrhage for which he received treatment with five sessions of plasma exchange. His symptoms resolved and cryocrit reduced to < 1% after his final dose of rituximab. The clinical features of cryoglobulinaemia may be difficult to detect in chronic haemodialysis patients and vigilance is required.

Evaluating LDL-C control in Indian acute coronary syndrome (ACS) patients- A retrospective real-world study LDL-C control in ACS.

Background: Low-density lipoprotein-cholesterol (LDL-C) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) progression. Although lipid lowering therapies remain the cornerstone of secondary ACSVD prevention, there exists residual dyslipidemia. The current study aimed to evaluate the real-world experience related to the treatment patterns and LDL-C control in Indian Acute Coronary Syndrome (ACS) patients. Methods: This was a real-world, descriptive, retrospective, observational, and multicentric study conducted across India. The data was collected for 1 year following the ACS event. The change in the levels of LDL-C from the baseline to the follow-up visits and the control of LDL-C, the change in lipid profile, lipoprotein levels, treatment patterns for lipid-lowering, and tolerability of existing treatments were evaluated. Results: Overall, 575 patients were included from 11 centers across India. The mean age of the patients was 52.92 years, with male predominance (76.35%). Although there was a significant reduction in the mean levels of LDL-C from the baseline [(122.64 ± 42.01 mg/dl to 74.41 ± 26.45 mg/dl (p < 0.001)], it was observed that despite high-intensity statin therapy, only 20.87% patients managed to achieve target LDL-C of <55 mg/dL and 55.65% were unable to reach LDL-C levels of <70 mg/dl one year after the event. Six patients reported adverse events without treatment discontinuation. Conclusion: The majority of the patients received high-intensity statins and did not attain target LDL-C levels, suggesting LDL-C control after an ACS event requires management with novel therapies having better efficacy as recommended by international and national guidelines.

Participant Perceptions in a Long-term Clinical Trial of Autosomal Dominant Polycystic Kidney Disease.

Rationale & Objective: The development of new therapies for autosomal dominant polycystic kidney disease requires clinical trials to be conducted efficiently. In this study, the factors affecting the recruitment and retention of participants enrolled in a 3-year randomized controlled trial in autosomal dominant polycystic kidney disease were investigated. Study Design: Qualitative study. Setting & Participants: All participants (N=187) were invited to complete a 16-item questionnaire at the final study visit of the primary trial. Participants were recruited to complete a semistructured interview using purposeful sampling according to age, self-reported gender, and randomization group. Analytical Approach: Descriptive statistics were used for demographic data and questionnaires. The interview transcripts underwent inductive thematic coding. Results: One hundred and forty-six of the 187 randomized participants (79%) completed the post-trial questionnaire, and 31 of the 187 participants (21%) completed the interview. Most participants (94%) rated their global satisfaction with the trial as high (a score of 8 or more out of 10). Altruism, knowledge gain, and access to new treatments were the main motivators for recruitment. The main reasons for considering leaving the study were concerns about the risk of intervention and family or work issues. Strategies that favored retention included flexibility in attending different study sites, schedule flexibility, staff interactions, and practical support with parking and reminders. The main burden was time away from work with lost wages, and burden associated with magnetic resonance imaging scans and 24-hour urine output collections. Limitations: The study population was restricted to participants in a single nondrug clinical trial, and the results could be influenced by selection and possible social desirability bias. Conclusions: Participants reported high levels of satisfaction that occurred as a function of the trial meeting participants' expectations. Furthermore, retention was a balance between the perceived benefits and burden of participation. Consideration of these perspectives in the design of future clinical trials will improve their efficiency and conduct. Plain-Language Summary: Advances in the clinical practice of autosomal dominant polycystic kidney disease (ADPKD) require affected individuals to voluntarily participate in long-term multicenter randomized controlled trials (RCTs). In this qualitative post hoc study of a 3-year RCT of increased water intake in ADPKD, altruism, knowledge gain, and access to a nondrug treatment positively influenced the decision to volunteer. Ongoing participation was enabled by building flexibility into the study protocol and staff prioritizing a participant's needs during study visits. Although participants completed the required tests, most were considered burdensome. This study highlights the importance of incorporating protocol flexibility into trial design; the preference for interventions with a low risk of adverse effects; and the urgent requirement for robust surrogate noninvasive biomarkers to enable shorter RCTs in ADPKD.

Comparison of glaucomatous from non-glaucomatous optic neuropathy using Bruch's membrane opening minimum rim width optical coherence tomography measurements.

Purpose: To compare glaucomatous from non-glaucomatous optic atrophy using optical coherence tomography (OCT) based on the measurement values of Bruch's membrane opening minimum rim width (BMO-MRW), which is a difficult task otherwise due to their varied course of disease progression, treatment protocols, and systemic association to visual impairment. Methods: This study was conducted in 40 eyes, comprising 20 eyes with non-glaucomatous optic neuropathy (NGON) and 20 eyes with glaucomatous optic neuropathy (GON). All patients underwent a complete ophthalmic examination followed by an OCT optic disc scan to calculate the measurement of BMO-MRW. Results: The 5-fold cross-validated area under the curve for GON versus NGON from logistic regression models was 0.95 (95% confidence interval [CI]: 0.86-1.00) using BMO-MRW values from all sectors. The results revealed that the measurements were significantly lesser in GON than in NGON patients. Conclusion: Hence, OCT-based BMO-MRW values could be used as an additional test to compare glaucomatous with non-glaucomatous optic neuropathy patients, especially in cases of high clinical suspicion.

Next-Generation Sequencing Highlights of Diffuse Large B-cell Lymphoma in a Tertiary Care Hospital in North India.

INTRODUCTION: Next-generation sequencing (NGS) elucidates the diffuse large B-cell lymphoma (DLBCL) genetic characteristics by finding recurrent and novel somatic mutations. This observational study attempted to create an NGS panel with a focus on identifying novel somatic mutations which could have potential clinical and therapeutic implications. This panel was created to look for mutations in 133 genes chosen on basis of a literature review and it was used to sequence the tumor DNA of 20 DLBCL patients after a centralized histopathologic review. METHODS: The study included 20 patients having DLBCL. The quality and quantity of tumor cells were accessed by H&E staining and correlated with histopathology and Immunohistochemistry (IHC) status. Patients were grouped as ABC (activated B-cell), PMBL (primary mediastinal large B-cell lymphoma), and other or unclassified subtypes. The lymphoma panel of 133 was designed on targeted sequencing of multiple genes for the coding regions through NGS. The libraries were prepared and sequenced using the Illumina platform. The alignment of obtained sequences was performed using Burrows-Wheeler Aligner and identification of somatic mutations was done using LoFreq (version 2) variant caller. The mutations were annotated using an annotation pipeline (VariMAT). Previously published literature and databases were used for the annotation of clinically relevant mutations. The common variants were filtered for reporting based on the presence in various population databases (1000G, ExAC, EVS, 1000Japanese, dbSNP, UK10K, MedVarDb). A custom read-depth-based algorithm was used to determine CNV (Copy Number Variants) from targeted sequencing experiments. Rare CNVs were detected using a comparison of the test data read-depths with the matched reference dataset. Reportable mutations were prioritized and prepared based on AMP-ASCO-CAP (Association for Molecular Pathology-American Society of Clinical Oncology-College of American Pathologists), WHO guidelines, and also based on annotation metrics from OncoMD (a knowledge base of genomic alterations). RESULTS: The informativity of the panel was 95 percent. NOTCH 1 was the most frequently mutated gene in 16.1% of patients followed by 12.9% who had ARID1A mutations. MYD88 and TP53 mutations were detected in 9.6% of the patient while 6.4% of patients had CSF3R mutations. NOTCH 1 and TP 53 are the most frequently reported gene in the middle age group (40-60). Mutation in MYD88 is reported in every age group. MYD88 (51%) is the most common mutation in ABC subtypes of DLBCL, followed by NOTCH 1 (44%) and SOCS 1 (33%) according to our findings. NOTCH 1 mutations are frequent in ABC and PMBL subtypes. Closer investigation reveals missense mutation is the most frequent mutation observed in the total cohort targeting 68.4% followed by frameshift deletion reported in 26.3%. Six novel variants have been discovered in this study. CONCLUSIONS: This study demonstrates the high yield of information in DLBCL using the NGS Lymphoma panel. Results also highlight the molecular heterogeneity of DLBCL subtypes which indicates the need for further studies to make the results of the NGS more clinically relevant.

Invasive Fungal Sinusitis in Patients With Coronavirus Disease 2019 Seen in South India.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a vast array of presentations and associations with neuro-ophthalmic diseases. There has been a recent surge in ophthalmic manifestations secondary to fungal sinus infections in India especially in diabetic patients who were given systemic steroids. We present our COVID-19-related cranial neuropathies presenting in our clinic. METHODS: This is a retrospective case series of 10 patients affected with COVID-19 disease and who presented with cranial nerve palsies at the neuro-ophthalmic department of a tertiary eye care hospital in South India. An analysis of electronic medical records data was performed, including their comorbidities, symptoms, cranial nerves involved, ocular and neuroimaging findings, site of lesion, etiology, and prognosis. RESULTS: Most of the patients (7 of 10) presented with multiple cranial nerve palsies (MCNP) with poor visual acuity. 2 of the 10 cases succumbed to death due to the intracranial involvement. All MCNP cases had uncontrolled diabetes with a history of systemic steroids, and neuroimaging of these cases showed sinusitis of varying severity most of which were suggestive of fungal invasive type. CONCLUSION: Our study emphasizes the need to screen for fungal involvement in COVID-19 cases presenting with MCNP especially on diabetic patients on systemic steroids so that an early diagnosis may reduce visual loss and mortality. Physicians treating COVID-19 cases need to be aware of this dreadful complication.

Hepatic Plasmacytoma With DEL13q14 Positive on Fluorescent In Situ Hybridization (FISH) on Tissue Biopsy.

A 40-year-old male presented with abdominal distension and dyspnea. On evaluation found to have hepatic plasmacytoma without marrow clonal plasma cells. Fluorescent in situ hybridization (FISH) on tissue biopsy revealed myeloma-defining cytogenetics. After treating with novel agents, the patient had a complete response to therapy.

Retinal manifestations in patients with SARS-CoV-2 infection and pathogenetic implications: a systematic review.

INTRODUCTION: The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a system-wide thromboembolic state, leading to serious cardiovascular, cerebrovascular and peripheral vascular manifestations. However, our knowledge regarding retinal manifestations due to systemic COVID-19 is minimal. This systematic review has comprehensively summarized all retinal manifestations secondary to COVID-19 disease recorded till date since the beginning of the pandemic. METHODS: All studies published till November 27, 2020, which have reported retinal manifestations in COVID-19 patients were systematically reviewed using the PRISMA statement. RESULTS: We included 15 articles: 11 case reports and four cross-sectional case series. The most commonly reported manifestations which did not affect visual acuity were retinal hemorrhages and cotton wool spots. The most common vision threatening manifestation was retinal vein occlusion with associated macular edema. Rarely, patients may also present with retinal arterial occlusions and ocular inflammation. These manifestations may occur from as soon as within a week after the onset of COVID-19 symptoms to more than 6 weeks after. CONCLUSION: Mostly causing milder disease, COVID-19 may however lead to severe life-threatening thromboembolic complications, and systemic antithrombotic therapy has been suggested as a prophylactic and therapeutic management strategy for patients affected with serious systemic disease. However, both sick and apparently healthy patients may suffer from various retinal complications which may lead to loss of vision as well. No consensus regarding management of retinal complications with anticoagulants or anti-inflammatory medications have been proposed; however, they may be tackled on individual basis.

Anatomical and functional features of photic retinopathy: a spectral domain optical coherence tomography-based longitudinal study.

BACKGROUND: Photic retinopathy may lead to permanent foveal structural injury, leading to irreversible visual acuity loss. METHOD: This prospective observational study evaluated 51 eyes of 30 patients with photic retinopathy. Optical coherence tomography (OCT) imaging was performed for all the eyes at baseline and final follow-up. All the eyes showed a focal outer retinal defect on spectral-domain OCT (SD-OCT) at the junction of the inner and outer photoreceptor segments. SD-OCT was used to measure central macular thickness, maximum horizontal dimension of the defect, maximum defect thickness, and the photic retinopathy index (PRI) through the foveal raster scan. RESULTS: Although PRI improved significantly at the final follow-up from baseline with a 17% improvement in PRI after a period of 6 months in photic retinopathy eyes, visual acuity declined for 14% of the patients and was stable for 84%. There was mild correlation of visual acuity with baseline PRI. Baseline PRI was significantly higher in eyes with poorer presenting visual acuity (VA). In total, 33.3% of the eyes showed partial ellipsoid zone recovery at 6 months. The area under curve of the receiver operator characteristic curve for partial ellipsoid zone recovery with the mean baseline PRI as the independent variable was poor at 0.612. CONCLUSION: OCT-based ultrastructural features in photic retinopathy seem to have poor correlation with presenting or final visual acuity. To the best of our knowledge, this is the largest study on longitudinal OCT evaluation of photic retinopathy eyes in literature.

Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Arginine vasopressin promotes kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Increased water intake reduces arginine vasopressin and urine osmolality and may slow kidney cyst growth. METHODS: In this randomized controlled 3-year clinical trial, we randomly assigned adults with ADPKD who had a height-corrected total kidney volume in Mayo imaging subclass categories 1B to 1E and an estimated glomerular filtration rate of 30 ml/min/1.73 m2 or greater to (1) water intake prescribed to reduce 24-hour urine osmolality to 270 mOsmol/kg or less or (2) ad libitum water intake irrespective of 24-hour urine osmolality. The primary end point was the percentage annualized rate of change in height-corrected total kidney volume. RESULTS: A total of 184 patients participated in either the ad libitum water intake group (n=92) or the prescribed water intake group (n=92). Over 3 years, there was no difference in the annualized rate of change in height-corrected total kidney volume between the ad libitum (7.8% per year; 95% confidence interval [CI], 6.6 to 9.0) and prescribed (6.8% per year; 95% CI, 5.8 to 7.7) water intake groups (mean difference, −0.97% per year; 95% CI, −2.37 to 0.44; P=0.18). The difference in mean 24-hour urine osmolality between the ad libitum and prescribed water intake groups was −91 mOsmol/kg (95% CI, −127 to −54 mOsmol/kg), with 52.3% of patients achieving adherence to the target 24-hour urine osmolality and no reduction in serum copeptin over 3 years. The frequency of adverse events was similar between groups. CONCLUSIONS: For patients with ADPKD, prescribed water intake was not associated with excess adverse events and achieved the target 24-hour urine osmolality for half of the patients but did not reduce copeptin or slow the growth of total kidney volume over 3 years compared with ad libitum water intake. (Funded by the National Health and Medical Research Council of Australia [grant GNT1138533], Danone Research, PKD Australia, the University of Sydney, and the Westmead Medical Research Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12614001216606).

Clinical features and surgical outcomes of complications of proliferative diabetic retinopathy in young adults with type 1 diabetes mellitus versus type 2 diabetes mellitus - A comparative observational study.

PURPOSE: To evaluate the clinical profile, visual outcomes, and complications among young adult patients with type 1 diabetes mellitus (insulin-dependent DM-T1DM) in comparison with patients with type 2 diabetes mellitus (T2DM) undergoing vitrectomy for complications of proliferative diabetic retinopathy (PDR).. METHODS: A retrospective review of patients between 18 and 45 years with T1DM undergoing vitrectomy for complications of PDR between June 2017 and June 2019, with a minimum follow-up of 12 months. Consecutive patients between 30 and 45 years with type 2 diabetes (non-insulin-dependent DM-T2DM) who underwent vitrectomy for the same indications were retrospectively enrolled as the control group. RESULTS: There were 42 eyes (28 patients) in the T1DM group and 58 eyes (47 patients) in the T2DM group. The average age at operation was 35.9 ± 6.88 years and 39.8 ± 3.03 years, respectively (P < 0.001). At the end of follow-up, the mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 1.53 ± 0.55 to 1.30 ± 0.93 (P value 0.07) in the T1DM group and from 1.59 ± 0.46 to 1.00 ± 0.78 in the T2DM group (P = 0.0001). The rate of the primary and final reattachment was 76.2% and 88.1% in the T1DM group and 84.5% and 96.6% in the T2DM group. Preoperative macular tractional retinal detachment (MTRD) and neovascular glaucoma (NVG) in both the groups, chronic kidney disease (CKD) and lack of preoperative Pan retinal photocoagulation (PRP) in the T1DM group, hypertension (HTN) and, resurgery in the T2DM group, were risk factors for poor vision at the final follow-up. CONCLUSION: The visual and anatomic outcomes were poorer in the T1DM patients which could be due to the longer duration of diabetes with worse glycemic control, associated comorbidities like CKD, and a higher incidence of MTRD.