Tofacitinib for Refractory Uveitis and Scleritis in Children: A Case Series.

PURPOSE: This study analyzes the efficacy and safety of tofacitinib in pediatric patients presenting with treatment-resistant uveitis and scleritis. METHOD: Retrospective Chart Review. RESULT: Nine children diagnosed with uveitis and one with scleritis received oral tofacitinib treatment. The median age of these patients was 9 years, with bilateral involvement observed in nine of them. Juvenile idiopathic arthritis was the most identifiable cause of uveitis, with anterior uveitis (50%) being the most frequent subtype of inflammation among these children. The median duration of immunosuppressive treatment before switching to tofacitinib was 18 (16-49) months. Remission of uveitis was achieved in all but two children, who experienced recurrence - manifesting as anterior uveitis. The median duration of follow-up in these children after tofacitinib treatment was 277.5 (183-549) days. At the end of follow-up, topical steroids could be withdrawn in six children, and two children were on topical steroids once a day. None of the children developed any systemic side-effect during the follow-up period. The mean BCVA at presentation was 0.62 ± 0.55, which improved to a mean of 0.27 ± 0.325 at the final follow-up (p = 0.0014). CONCLUSION: Treatment of pediatric uveitis with tofacitinib can be a valuable second-line treatment option and useful alternative in low- and middle-income countries.

Role of eccentric viewing training with microperimeter for low vision rehabilitation in multifocal choroiditis: Case report.

A 21-year-old student with healed multifocal choroiditis involving the macula presented with difficulty in seeing distance and reading her college books. Based on microperimetr'y, the location of her preferred retinal locus and the position of new trained retinal locus (TRL) were identified. With multiple sessions of biofeedback training, her mean retinal sensitivity improved from 4.8 to 8.8 dl, distance vision from 3/60 to 6/36, and near vision from N32 to N8 in the right eye. At 6-month follow-up, her TRL position and visual acuity were found to be stable. This case report highlights that eccentric viewing training using microperimeter can significantly improve the efficiency of functional vision in patients with choroiditis.

Demystifying Ocular Syphilis - A Major Review.

Syphilis, caused by the spirochaete, Treponema pallidum, continues to be a public health challenge globally with its rates steadily increasing in the past few years. The disease is transmitted through small breaks in the skin during sexual contact, or via congenital transmission in utero, either across the placenta or by contact with an active genital lesion during delivery. Estimated 5.7-6 million new cases are detected every year worldwide in the 15-49 years age group. An increased incidence has been reported in most populations with particular clusters in special groups like men who have sex with men, female sex workers, and their male clients. Ocular syphilis has a varied presentation and is considered a great mimicker in all cases of uveitis. The laboratory diagnosis of syphilis is predominantly based on serological tests including TPHA and VDRL. Parenteral penicillin is the cornerstone of treatment for all stages of ocular syphilis.

Differential Expression of miRNA-192 is a Potential Biomarker for HIV Associated Immune Recovery Uveitis.

PURPOSE: Notwithstanding well-established clinical features of Immune Recovery Uveitis (IRU), specific diagnostic tools to identify at-risk patients are lacking. Identification of biomarkers for IRU prediction can allow high-risk patients to benefit from specific preventive strategies, development of therapies, and elucidate immune reconstitution associated pathogenesis. METHODS: HIV+ patients were classified into four groups (A, B, C and D) with and without ocular manifestations, with follow-up over a year. Patients' ocular parameters were examined and manifestations like uveitis and IRU noted. Selected miRNAs were investigated in PBMCs by using miRNA PCR assay. Bioinformatic analysis used miRNet to predict the targets of miRNA-192-5p and miRNA-543 and KOBAS for pathways. RESULTS: Hsa-miR-192-5p and hsa-miR-543 levels were measured by qPCR using RNA isolated from PBMCs of HIVinfected patients. Hsa-miR-192-5p and hsa-miR-543 were down regulated in patients exhibiting ocular manifestations. Our results showed hsa-miR-192-5p (Group B vs D p 0.007) and hsa-miR-543 levels in PBMCs reliably distinguish between HIV patients diagnosed with IRU. Both miRNAs target multiple genes involved in inflammatory pathways as predicted by bioinformatic analysis. CONCLUSION: Decreased expression levels of miRNA-192 in patients with ocular manifestations and IRU, could facilitate identification of the status of the disease in HIV patients.

Impact of COVID-19 pandemic on uveitis patients receiving immunomodulatory and biological therapies (COPE STUDY).

PURPOSE: To evaluate the change in the ongoing immunomodulatory (IMT) and biological therapies among patients with non-infectious uveitis (NIU), and determine the number of uveitis relapses during the COVID-19 pandemic. METHODS: In this national multicentric prospective case series, data of subjects with NIU receiving corticosteroids, systemic IMT and/or biological agents were analysed. The data collection was performed from 1 March 2020 to 25 June 2020. Main outcome measures included change in the ongoing treatments with corticosteroids, IMT and biological agents, use of alternate therapies and rates of uveitis relapse. RESULTS: In this study, 176 patients (284 eyes) with NIU (mean age: 33±17.1 years; males: 68) were included. A total of 121 eyes (90 patients) were deemed to have active NIU. Of these, seven subjects (7.8%) did not receive intravenous methylprednisolone despite need felt by the treating uveitis experts. In addition, 35 subjects (57.4%) received a rapid tapering dosage of oral corticosteroids despite active disease. A total of 161 (91.5%) subjects were receiving systemic IMT and 25 (14.2%) were on biological therapies. Overall, IMT was altered in 29/161 (18.0%) subjects. Twenty-two eyes were treated with intravitreal therapies in the study period. Fifty-three eyes (32.5%, 29 subjects) developed relapse of NIU, of which 25 subjects (86.2%) were deemed to have reactivation related to altered systemic IMT. No patient developed COVID-19 during follow-up. CONCLUSIONS: During the ongoing COVID-19 pandemic, uveitis specialists may tend to reduce the ongoing systemic IMT, or prefer less aggressive treatment strategies for NIU. These subjects may be at high risk of relapse of uveitis.

Utility of Treponemal Testing from Aqueous Fluid in the Diagnosis of Ocular Syphilis in Patients with HIV/AIDS.

PURPOSE: Ocular syphilis is re-emerging globally especially in patients with human immunodeficiency virus (HIV). Atypical manifestations of ocular syphilis and/or other associated opportunistic infections often lead to a diagnostic dilemma. We evaluated the utility of aqueous humor (AH) Treponema pallidum hemagglutination assay (TPHA) titers in the diagnosis of ocular syphilis. METHODS: Retrospective case series of five HIV positive patients with positive syphilis serology in whom AH sampling was performed. All patients had ocular manifestations suspicious of infectious etiology. RESULTS: Panuveitis with/without retinitis was the commonest presentation. Along with blood investigations, polymerase chain reaction (PCR) testing from AH was done for Mycobacterium tuberculosis (MTB), Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), and Toxoplasma gondii. In addition, serum antibody titers for Toxoplasma, rapid plasma reagin (RPR) and TPHA tests for syphilis were done. In patients with raised serum RPR/TPHA, aqueous TPHA titers were also assessed. Mean serum RPR titer was ≥ 1:32 and TPHA titer was ≥1:1280. Aqueous humor titers of TPHA was high in all patients (range ≥ 1:320 to ≥1:5120). Aqueous PCR was negative for all other infectious etiologies in four patients. In one patient, PCR-CMV was also positive, suggestive of a dual infection. Post-treatment with highly active antiretroviral therapy (HAART) and appropriate anti-syphilitic regime, complete resolution of lesions with corresponding fall in the serum RPR/TPHA titers were noted in all patients. CONCLUSIONS: Ocular syphilis with atypical presentations is usually diagnosed based on a positive syphilis serology and by excluding other infectious causes. In the present study, we have shown an excellent correlation between raised AH TPHA titers with serological values and the clinical presentation. Considering the ease of collection of AH in contrast to vitreous fluids, the AH-TPHA assay could potentially be a valuable tool in the diagnosis of ocular syphilis.

Choroidal neovascularization in 111 eyes of children and adolescents.

PURPOSE: To describe the clinical features, management, and outcomes of choroidal neovascularization (CNV) in children less than 18 years of age. METHODS: This was a retrospective, case control study of 111 eyes of 96 patients. CNV was clinically diagnosed in all patients. Eyes were classified as those that were observed (Controls; Group 1) or those that had treatment (Cases; Group 2). CNV was categorized as regressed, persistent, or recurrent in order to evaluate the anatomical outcomes. RESULTS: Of 96 patients, 68(71%) were male. Mean presenting age was 11.4 ± 3.4 years (median = 11 years, range = 1-17 years). CNV was bilateral in 15(16%) patients. Of 111 eyes, 38 eyes had treatment (Cases) and 73 eyes did not (Natural history group or Controls). Subfoveal CNV was seen in majority of cases (59%). Most common etiology was post-inflammatory (38%), followed by trauma (16%). Eyes were classified as those that were observed (controls; Group 1) or those that had treatment (cases; Group 2). In group 1, spontaneous regression of CNV was seen in 26(36%) eyes and there was no recurrence in this group. In group 2 following treatment, 25(66%) of 38 eyes achieved complete regression at mean 4.9 months and was persistent in 5 eyes. CNV recurrence was seen in 10 eyes with the mean time to first recurrence being 9 months. At presentation, mean best-corrected visual acuity (BCVA) of eyes with subfoveal CNV was logMAR 0.99 that improved to logMAR 0.63 with treatment. Mean follow-up was 17 months. CONCLUSION: CNV results in significant visual decline in children; most commonly of post-inflammatory etiology. Treatment achieves high regression rates, albeit with limited visual improvement.

Cataract Surgery in the Setting of Scleritis.

Purpose: To report the clinical profile of cataract and its surgical management in a scleritis cohort from India.Methods: We conducted a retrospective review of medical records of 39 eyes of 32 consecutive patients with scleritis who underwent cataract surgery in a tertiary eye care institute.Results: The mean age at presentation was 50.9 ± 11.1 years and 65.6% of the patients were female. Five patients (15.6%) were ≤ 40 years of age. Necrotizing scleritis (56.4%) was the most common subtype of scleritis in this cohort followed by diffuse anterior scleritis (28.2%), nodular scleritis (12.8%). The preferred incision for phacoemulsification was clear corneal in 30 eyes (77%). In the immediate post-operative period, four eyes (10.2%) developed severe corneal edema, one eye had descemet membrane detachment. Anterior chamber reaction was observed in 18 eyes (46.1%). Fifteen eyes (38.4%) developed raised intraocular pressure and two required surgical intervention after 3 months of cataract surgery. Early posterior capsular opacification was observed in 5 eyes (12.8%) and cystoid macular edema in 2 eyes (5.1%).Conclusion: In addition to providing a distinct pattern of cataract, index study showed that long-term control of scleral inflammation prior to the cataract surgery remains the primary requisite for the successful outcome.

Efavirenz-Associated Retinal Toxicity Presenting with Night Vision Defects in Patients with Human Immunodeficiency Virus.

Ocular lesions in patients with human immunodeficiency virus (HIV) are commonly due to underlying opportunistic infections. With highly active antiretroviral therapy (HAART), infectious lesions have reduced and noninfectious ocular manifestations including drug-related side effects have been noted. While retinal toxicity has been noted with few other HAART drugs, there are not many on the same with Efavirenz usage. We report a series of five patients with possible efavirenz-related retinal toxicity, visual function abnormalities, and its management. Efavirenz was replaced with alternate anti-retroviral drug. Reversal of ocular side effects were noted subjectively in the form of symptom amelioration of the patients. Objectively, it could be documented with electroretinogram changes and other visual function tests reverting back to normal after change in HAART regime. Early identification of this uncommon side effect in select patients can prevent irreversible vision loss due to efavirenz-associated retinal toxicity.

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update.

Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.

Ocular syphilis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome in the era of highly active antiretroviral therapy.

PURPOSE: Re-emergent ocular syphilis in patients with Human immunodeficiency virus (HIV) co-infection has both diagnostic and management difficulties because of the overlapping risk factors. The clinical manifestations described in non-HIV may not be the same in patients with HIV coinfection. Immune recovery uveitis (IRU) may also alter the course of the disease causing recurrences. We studied the clinical features in correlation with CD4 counts, systemic immune status, sexual preferences and management outcomes in HIV/AIDS patients with ocular syphilis in the highly active antiretroviral treatment (HAART) era from a high endemic HIV population like India. METHODS: Retrospective analysis of all patients with ocular syphilis and HIV/AIDS seen between 2016 and 2019 was done. RESULTS: A total of 33 patients (56 eyes) with a CD4 count range of 42-612 cells/cu.mm were included. Ocular syphilis was found to be higher in individuals with high risk behavior such as men who have sex with men (MSMs) (45%). Panuveitis was the commonest manifestation (53.57%) and was even the presenting feature of HIV and syphilis in many patients. Significant vitritis, usually uncommon in HIV/AIDS immunocompromised patients was noted even with low CD4 counts in patients with ocular syphilis. Significant correlation was noted between ocular presentation and CD4 counts (P < 0.05). CONCLUSION: Ocular syphilis presents differently in patients with HIV/AIDS. Diffuse retinitis is seen commonly in low counts (<100 cells/cu.mm). Classical placoid chorioretinitis lesions usually described in non-HIV individuals is uncommon in HIV patients and is seen in higher CD4 counts ( >400 cells/cu.mm). Ocular manifestations can be an indicator of the immune status of the patient. Not all patients with ocular manifestations have associated features of systemic syphilis. Ocular manifestations can be the first presentation of HIV/AIDS. Although, there is good response to systemic penicillin and HAART, recurrences and immune recovery uveitis (IRU) can also occur.

Clinical profile of patients with anterior nodular scleritis in India.

PURPOSE: To report the clinical profile of a series of anterior nodular scleritis in Indian population. METHODS: We conducted a retrospective review of medical records of 140 eyes of 123 consecutive patients with nodular scleritis who presented to a tertiary eye care institute between 2007 and 2018. RESULTS: The mean age at presentation was 46.8 ± 13.1 years and 70.7% of the patients were female. Bilateral involvement was observed in 14% patients. The most common presenting symptom was redness (92.6%) and ocular pain (69.1%). Twenty-seven patients (22%) had some systemic association and rheumatoid arthritis (5%) was the most common autoimmune disease. Presumed ocular tuberculosis was diagnosed in 13% patients. Methotrexate was the most common immunosuppressive used in these patients and an additional immunosuppressive was required in 6.5% patients. Recurrence of inflammation was observed in 74.8% patients. Deterioration of vision noted in 2.8% eyes. CONCLUSION: Tuberculosis remains an important cause of nodular scleritis in India. Recurrence of scleritis is common in nodular scleritis and cases with non infectious nodular scleritis often require treatment with immune suppressives.

Ocular Surface Disorders in Patients with Human Immunodeficiency Virus (HIV) Infection.

Purpose: To describe ocular surface disorders associated with human immunodeficiency virus (HIV). Methods: Narrative review. Results: Ocular surface neoplastic conditions, such as Kaposi's sarcoma, conjunctival lymphoma and ocular squamous cell carcinoma along with blepharitis, dry eye disease, and vernal keratoconjunctivitis, constitute ocular surface complications in HIV-infected individuals. Conclusion: This review will provide a summary of clinical presentations and treatment options for the most common HIV-related ocular surface diseases, indicating the need for a comprehensive ocular examination including ocular surface in all HIV patients 22.

Clinical and electrophysiological characteristics of Efavirenz-induced macular toxicity.

Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, is commonly used to treat HIV-infected individuals. We report a case of painless, progressive and bilateral blurring of vision in an HIV-positive 54-year-old lady within months of treatment with anti-retro viral therapy including Efavirenz. On presentation, her visual acuity was 6/18; N24 and 6/9; N10 in both eyes with mottling of the retinal pigment epithelial at the macula with corresponding scotomas on HVF 30-2 and loss of ellipsoid layer on spectral domain optical coherence topography (OCT). Though full field ERG was normal, multifocal ERG revealed reduced foveal and parafoveal amplitudes. Our case emphasizes the need of periodic ocular examination of these patients on long-term EFV.

Paradoxical reactions in ocular tuberculosis.

Paradoxical reactions following initiation of anti-tubercular therapy have been documented most often in extrapulmonary tuberculosis. A combination of factors such as delayed hypersensitivity, decreased suppressor mechanisms, and an increased response to mycobacterial antigens mediated by the host's immune system have been implicated in the development of these reactions. Similar worsening in patients with ocular tuberculosis while on treatment has been described. It is therefore important for the clinician to be aware of this occurrence, as prompt recognition and timely institution of corticosteroids and immunosuppressants can lead to restoration of vision. In these patients, an alteration or discontinuation of anti-tubercular therapy may not be indicated.

Clinical profile of uveitis patients developing central serous chorioretinopathy: An experience at a tertiary eye care center in India.

PURPOSE: To evaluate clinical profile of patients with uveitis who developed central serous chorioretinopathy (CSC). METHODS: Retrospective case series of consecutive patients of uveitis with CSC managed at a tertiary eye care center in India between 1994 and 2014. The data about clinical features, investigations, treatment, and outcomes were obtained from their medical records. RESULTS: A total of 31 eyes of 26 patients with uveitis with a diagnosis of CSC between June 1994 and May 2014 were included in the study. The mean age of presentation was 42.8 ± 9.2 years, and 88.4% of the patients were male. CSC was bilateral in 19.2% of the patients, and in 38.4% patients uveitis was because of infectious etiology. CSC developed in 23 (88.5%) patients when they were on oral corticosteroid. The most common cause of uveitis in our study was choroiditis (48.4%), followed by retinal vasculitis (12.9%). The mean time for resolution of CSC was relatively less in patients with uveitis because of infectious etiology. In 10% eyes vision remained the same and deterioration of vision was noted in 19% eyes. Best corrected visual acuity of the patients at the time of presentation with CSC was 0.56 ± 0.34 and after the resolution of CSC was 0.48 ± 0.5 (P < 0.0005). CONCLUSION: Patients with choroidal inflammations are more prone to develop CSC compared with other subtypes of uveitis. Management of CSC in uveitis can be challenging.

Visual rehabilitation of patients with low vision in uveitis.

PURPOSE: To elucidate the clinical profile of visual impairment (VI) and rehabilitation of the uveitic patients with irreversible low vision. METHODS: Retrospective analysis of visual rehabilitation of patients with uveitis suffering from poor vision with low vision devices (LVD). RESULTS: Most common cause of uveitis was choroiditis (46.29%), followed by retinitis (25.92%), retinochoroiditis (18.51%), and chronic panuveitis sequelae (9.25%). Of these 54 cases, 35.18% had moderate VI, 25.92% had severe VI, 20.37% had mild VI, and 18.51% had profound VI or blindness. Statistically significant improvement (P < 0.05) in near vision was seen in choroiditis (52%) and retinitis (72%), whereas clinically significant improvement in distance vision was found in patients with choroiditis. Most commonly prescribed LVD was half-eye prismatic spectacle magnifier (22.2%). CONCLUSION: Rehabilitation of the uveitic patients with low vision is challenging. LVD may be a beneficial tool in these patients to help them perform their day-to-day activities independently.