Shruti Sinha, Rohan Bir Singh, Thomas H Dohlman, Mengyu Wang, Yukako Taketani, Jia Yin, and Reza Dana. 2020. “Prevalence of Persistent Corneal Epithelial Defects in Chronic Ocular Graft-Versus-Host Disease.” Am J Ophthalmol, 218, Pp. 296-303.Abstract
PURPOSE: To establish the prevalence, clinical characteristics, and risk factors for persistent corneal epithelial defects (PED) in patients with chronic ocular graft-versus-host disease (oGVHD) and to determine visual outcomes after healing. DESIGN: Retrospective cohort study. METHODS: A chart review was conducted of patients in whom chronic oGVHD was diagnosed between January 2011 and December 2018 and their demographic and clinical characteristics were collected. Data were analyzed to determine prevalence of PED, and multivariate logistic regression was performed to determine the risk factors associated with it. RESULTS: A total of 405 patients at a mean age of 60 ± 13 years in whom chronic oGVHD was diagnosed; 58% were men. The prevalence of PED was 8.1%. The median time for PED development after hematopoietic stem cell transplantation was approximately 24 months. Median time to PED resolution was 4.5 weeks after starting therapy. The mean best-corrected visual acuity declined by 2 lines post-PED resolution. The prevalence rates of corneal ulcer and perforation were 6.2% and 4.0%, respectively, over 8 years. Logistic regression analysis, used to determine factors associated with PED, showed diabetes (P = .006), limbal stem cell deficiency (LSCD) (P = .02), filamentary keratitis (P = .02), subconjunctival fibrosis (P = .02), and a higher National Institutes of Health (NIH) oGVHD score (P = .01) were significant risk factors for PED development. CONCLUSIONS: The study found the prevalence rate of PED, corneal ulceration, and corneal perforation in chronic oGVHD to be 8.1%, 6.2%, and 4%, respectively. Analysis showed that oGVHD patients with diabetes, LSCD, filamentary keratitis, subconjunctival fibrosis, and a high NIH score were at higher risk of developing severe corneal disease.
Rohan B Singh, Parul Ichhpujani, Sahil Thakur, and Sumeet Jindal. 2020. “Promising therapeutic drug delivery systems for glaucoma: a comprehensive review.” Ther Adv Ophthalmol, 12, Pp. 2515841420905740.Abstract
The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include-inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment.
Rohan Bir Singh, Shruti Sinha, Chhavi Saini, Elsayed Elbasiony, Sahil Thakur, and Aniruddha Agarwal. 2020. “Recent advances in the management of non-infectious posterior uveitis.” Int Ophthalmol, 40, 11, Pp. 3187-3207.Abstract
PURPOSE: To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU). METHODS: We performed a thorough review of current literature using PubMed, Google Scholar and to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials. RESULTS: The current management regimen for non-infectious posterior uveitis includes corticosteroids, immunomodulatory therapies and anti-metabolites. However, NIPU requires long-term management for efficacious remission of the disease and to prevent disease relapse. Long-term safety issues associated with steroids have led to efforts to develop novel therapeutic agents including biological response modulators and immunosuppressants. The current therapeutic agents in various stages of development include calcineurin inhibitors, biologic response modifiers and a more a comprehensive modalities like ocular gene therapy as well as novel drug delivery mechanisms for higher bioavailability to the target tissues, with minimal systemic effects. CONCLUSION: Novel efficacious therapeutic modalities under development will help overcome the challenges associated with the traditional therapeutic agents.
Yukako Taketani, Anna Marmalidou, Thomas H Dohlman, Rohan Bir Singh, Afsaneh Amouzegar, Sunil K Chauhan, Yihe Chen, and Reza Dana. 2020. “Restoration of Regulatory T-Cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor.” Am J Pathol, 190, 9, Pp. 1859-1866.Abstract
Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity.
Jayesh Vira, Alessandro Marchese, Rohan Bir Singh, and Aniruddha Agarwal. 2020. “Swept-source optical coherence tomography imaging of the retinochoroid and beyond.” Expert Rev Med Devices, 17, 5, Pp. 413-426.Abstract
: Swept-source optical coherence tomography (SS-OCT) imaging has ushered in an era of rapid and high-resolution imaging of the retinochoroid that provides detailed patho-anatomy of various layers.: In this detailed review, the technology of swept-source imaging including its principles and working has been discussed. The applications of SS-OCT in various conditions including age-related macular degeneration, diabetic retinopathy, pachychoroid spectrum of diseases, and inflammatory vitreoretinal conditions have been elaborated. For each disease, a brief review of literature along with the utility of SS-OCT and optical coherence tomography angiography has been provided with supporting figures. The advantages of SS-OCT over spectral-domain have been discussed if there is sufficient evidence in the literature. Finally, the review summarizes the technological advantages in this field of retinal imaging.: The introduction of SS-OCT in our clinics has added newer devices in our armamentarium that can provide high-quality images of the deep retina and choroid. These advances in medical devices can help in improving our knowledge relating to the pathophysiology of diseases and their evolution. In the near future, rapid and high-resolution imaging may provide real-time volumetric information of the whole retina and the choroid that can be readily used for patient care.
Rohan Bir Singh, Chhavi Saini, Sukhman Shergill, and Aniruddha Agarwal. 2020. “Window to the circulatory system: Ocular manifestations of cardiovascular diseases.” Eur J Ophthalmol, 30, 6, Pp. 1207-1219.Abstract
The changes in the cardiovascular system are associated with ocular manifestations, often as a consequence of pathological alteration in the ocular vasculature. The ease of visualization of these retinal changes makes the eye a window to the cardiovascular system. Certain congenital cardiac defects lead to changes in the retinal vascularity due to increased tortuosity and dilatation. In adults, the arterial dissection of internal carotid and vertebral arteries present as amaurosis fugax with or without oculo-sympathetic palsy. The patients with untreated infective endocarditis present with Roth spots, retinitis, embolic retinopathy, or sub-retinal abscesses. Hypoperfusive, hypertensive, or "mixed" retinopathy is a hallmark sign in patients of untreated infective endocarditis. Giant cell arteritis can present with ischemic ocular symptoms that may precipitate in irreversible vision loss. Systemic vascular manifestations such as coronary artery disease may manifest in a wide range of symptoms from amaurosis fugax to vision loss depending upon the size and location of retinal emboli. Rare cardio-oncological pathologies such as myxomas result in vision loss secondary to central retinal artery occlusion. A high clinical suspicion in patients with history of cardiovascular diseases can help in early diagnosis and management of impending, adverse cardiovascular and cerebrovascular events. In this review, we comprehensively discuss the spectrum of cardiac and vascular diseases with ocular manifestations as well as highlight the typical ocular presentations associated with these pathologies.
Rohan Bir Singh, Sukhman Shergill, Kanwar Partap Singh, and Sahil Thakur. 2019. “Down and out: acquired oculomotor nerve palsy.” BMJ Case Rep, 12, 8.
Jia Yin, Rohan Bir Singh, Rani Al Karmi, Ann Yung, Man Yu, and Reza Dana. 2019. “Outcomes of Cyanoacrylate Tissue Adhesive Application in Corneal Thinning and Perforation.” Cornea, 38, 6, Pp. 668-673.Abstract
PURPOSE: To report the outcomes of cyanoacrylate tissue adhesive (CTA) application in corneal thinning and perforation. METHODS: A retrospective interventional case series of 137 patients receiving CTA for corneal thinning and perforation in 140 eyes between 2001 and 2018 at a single center was reviewed. Success rate and factors associated with glue failure were analyzed. RESULTS: Median age of the cohort was 63 years and 69 (50%) were women. One hundred fifteen patients (84%) had at least 1 systemic condition, 46 (34%) had autoimmune diseases. Eighty-nine eyes (64%) presented with perforation and 51 (36%) with thinning. The perforation/thinning was central/paracentral in 82 eyes (59%) and peripheral in 57 eyes (41%). Median size of perforation was 3.1 mm. Causes of perforation and thinning were microbial infection in 75 (55%), sterile melt in 49 (35%), laceration in 10, and keratoprosthesis melt in 8 eyes. Median glue retention was 58 days. Success rate of glue application (defined as intact globe without surgical intervention) was 72%, 61%, and 46% at 10, 30, and 90 days after glue application, respectively. Larger size of perforation/thinning, perforation (vs. thinning), and single glue application (vs. multiple) were correlated with higher failure rate. Systemic conditions, use of topical corticosteroid, etiologies, and location of perforation/thinning were not significantly correlated with glue failure. CONCLUSIONS: CTA application was moderately effective in stabilizing corneal perforation and thinning in the very short-term. Multiple applications are often required. Maintenance of globe integrity after glue application decreases with time and the need for surgical intervention remains high.
William Foulsham, Thomas H Dohlman, Sharad K Mittal, Yukako Taketani, Rohan Bir Singh, Sharmila Masli, and Reza Dana. 2019. “Thrombospondin-1 in ocular surface health and disease.” Ocul Surf, 17, 3, Pp. 374-383.Abstract
Thrombospondin 1 (TSP-1) is an extracellular matrix protein that interacts with a wide array of ligands including cell receptors, growth factors, cytokines and proteases to regulate various physiological and pathological processes. Constitutively expressed by certain ocular surface tissues (e.g. corneal and conjunctival epithelium), TSP-1 expression is modulated during ocular surface inflammation. TSP-1 is an important activator of latent TGF-β, serving to promote the immunomodulatory and wound healing functions of TGF-β. Mounting research has deepened our understanding of how TSP-1 expression (and lack thereof) contributes to ocular surface homeostasis and disease. Here, we review current knowledge of the function of TSP-1 in dry eye disease, ocular allergy, angiogenesis/lymphangiogenesis, corneal transplantation, corneal wound healing and infectious keratitis.
Parul Ichhpujani, Rohan Bir Singh, William Foulsham, Sahil Thakur, and Amtoj Singh Lamba. 2019. “Visual implications of digital device usage in school children: a cross-sectional study.” BMC Ophthalmol, 19, 1, Pp. 76.Abstract
PURPOSE: To evaluate the use of digital devices, reading habits and the prevalence of eyestrain among urban Indian school children, aged 11-17 years. METHODS: The study included 576 adolescents attending urban schools who were surveyed regarding their electronic device usage. Additional information on the factors that may have an effect on ocular symptoms was collected. RESULTS: Twenty percent of students aged 11 in the study population use digital devices on a daily basis, in comparison with 50% of students aged 17. In addition to using these devices as homework aids, one third of study participants reported using digital devices for reading instead of conventional textbooks. The majority of students preferred sitting on a chair while reading (77%; 445 students), with only 21% (123 students) preferring to lie on the bed and 8 students alternating between chair and bed. There was a significant association between the students who preferred to lie down and those who experienced eyestrain, as reported by a little over one fourth of the student population (27%). Out of 576 students, 18% (103) experienced eyestrain at the end of the day after working on digital devices. CONCLUSIONS: The increased use of digital devices by adolescents brings a new challenge of digital eyestrain at an early age. Our study reports the patterns of electronic device usage by school children, evaluates factors associated with eyestrain and highlights the need for further investigation of these issues.
Rohan Bir Singh, Sahil Thakur, and Kanwar Partap Singh. 2018. “Blueberry eye: acquired total anterior staphyloma.” BMJ Case Rep, 2018.
Rohan Bir Singh, Sahil Thakur, Parul Ichhpujani, and Suresh Kumar. 2018. “Ethics of a therapeutic trial: addressing limitations of an active intervention in optic nerve lymphoma.” BMJ Case Rep, 2018.Abstract
We report a unique case of optic nerve lymphoma after completion of chemotherapy for non-Hodgkin's lymphoma. The uncommon nature of presentation, our therapeutic dilemma and the further course of treatment are reported. In cases with extremely poor prognosis, unnecessary treatment puts additional strain both financially and psychologically on the patients and their family. Therapeutic focus should be on hospice care and family counselling. The decision to not treat is a crucial component of cancer management; however, the ethics of this decision are yet to be suitably addressed by the literature.
Rohan Bir Singh and Priti Batta. 2018. “Herpes simplex virus keratitis mimicking Acanthamoeba keratitis: a clinicopathological correlation.” BMJ Case Rep, 2018.Abstract
A 36-year-old male, soft contact lens wearer was referred by his primary ophthalmologist for corneal ulcer of the right eye (OD), which was persistent despite topical fluoroquinolone therapy for 1 month. A ring-shaped infiltrate typically seen in Acanthamoeba infection was noted, and topical therapy with chlorhexidine and polyhexamethylene biguanide was initiated. However, the patient's condition deteriorated over the next several weeks; thus, diagnostic and therapeutic penetrating keratoplasty was performed. The postoperative immunohistochemical analysis suggested a diagnosis of herpes simplex virus (HSV) keratitis. The patient ultimately improved after initiation of oral valacyclovir following penetrating keratoplasty. We report a case of a commonly encountered clinical entity, HSV keratitis, with an atypical clinical presentation, masquerading as Acanthamoeba keratitis.
Parul Ichhpujani, Sahil Thakur, Suresh Kumar, and Rohan B Singh. 2018. “Juvenile Open Angle Glaucoma With Nonbullous Congenital Ichthyosiform Erythroderma.” J Glaucoma, 27, 11, Pp. e180-e182.Abstract
INTRODUCTION: Glaucoma in patients with nonbullous congenital ichthyosiform erythroderma (NBCIE) is a rare entity that has not been described in a histologically confirmed case. We present a unique case of coexisting glaucoma, ichthyosis, and dwarfism that has not been previously described. METHODS: We present a case of NBCIE with glaucoma and dwarfism that presented to our outpatient department. The patient was referred for watering and photophobia that were due to an epithelial defect that was subsequently managed conservatively. Investigations revealed the existence of a constellation of findings that are presented here. RESULTS: NBCIE, glaucoma, and dwarfism represent a spectrum of diseases that seem to have a syndromic association. More gene linkage-based analysis are, however, needed to further confirm our observations. CONCLUSIONS: NBCIE, glaucoma, and dwarfism can often occur together and need to be assessed and managed individually. Early diagnosis of this spectrum can help improve patient management and quality of life. Dermatologists must get an ocular examination conducted for icthyoses patients.
Suresh Kumar, Parul Ichhpujani, Sahil Thakur, and Rohan Bir Singh. 2018. “Traumatic corneal perforation with exteriorisation of Ahmed glaucoma valve tube.” BMJ Case Rep, 2018.Abstract
We report a rare case of traumatic corneal perforation with Ahmed glaucoma valve (AGV) tube. A 5-year-old female child, diagnosed with refractory glaucoma, had undergone AGV implantation, presented with the posterior migration of AGV tube after trauma to the eye. The detailed ocular history, ophthalmic findings, clinical course and surgical management are discussed.
Rohan Bir Singh, Sahil Thakur, and Parul Ichhpujani. 2018. “Traumatic rosette cataract.” BMJ Case Rep, 11, 1.
Aniruddha Agarwal, Alessandro Invernizzi, Rohan Bir Singh, William Foulsham, Kanika Aggarwal, Sabia Handa, Rupesh Agrawal, Carlos Pavesio, and Vishali Gupta. 2018. “An update on inflammatory choroidal neovascularization: epidemiology, multimodal imaging, and management.” J Ophthalmic Inflamm Infect, 8, 1, Pp. 13.Abstract
Inflammatory choroidal neovascular membranes are challenging to diagnose and manage. A number of uveitic entities may be complicated by the development of choroidal neovascularization leading to a decrease in central visual acuity. In conditions such as punctate inner choroidopathy, development of choroidal neovascularization is extremely common and must be suspected in all cases. On the other hand, in patients with conditions such as serpiginous choroiditis, and multifocal choroiditis, it may be difficult to differentiate between inflammatory choroiditis lesions and choroidal neovascularization. Multimodal imaging analysis, including the recently introduced technology of optical coherence tomography angiography, greatly aid in the diagnosis and management of inflammatory choroidal neovascularization. Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy.
Parul Ichhpujani and Rohan B Singh. 2014. “Pediatric genetic diseases causing glaucoma.” J Pediatr Genet, 3, 4, Pp. 209-18.Abstract
Glaucomatous optic neuropathy may be considered as an endpoint of multiple systemic factors. Genetic conditions commonly causing glaucoma in children and adolescents include Axenfeld-Reiger syndrome, aniridia, Marfan syndrome, Weill-Marchessani syndrome, Sturge-Weber syndrome, Rubinstein-Taybi syndrome, nevus of Ota, congenital rubella and neurofibromatosis type 1. In the recent years, with the advancements in genetic research our understanding of the fundamental causes of glaucoma associated with inherited disorders has improved. In addition to intraocular pressure reduction, it is important for the clinician to be familiar with the multiple systemic associations with glaucoma, to re-evaluate treatment frequently, and to target the underlying disease process, if present.
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