Oral fluorescein angiography in the diagnosis of paediatric optic nerve abnormalities.

OBJECTIVE: FFA is a well-established investigation for the diagnosis of optic nerve abnormalities, requiring an intravenous cannula and extended imaging acquisition time. Cannulation can present a challenge in paediatric patients and whilst oral FFA has been used for decades, it has been limited by imaging technology and unconfirmed image acquisition timings. For years, we have used a modern ultra-widefield retinal camera, and established imaging time-points to demonstrate dynamic optic nerve head changes upon ingestion of fluorescein and collected a database of oFFA images for various presentations. METHODS: Using an established protocol, optic nerve colour images were obtained, followed by oral administration of fluorescein dye. The optic nerves are then imaged at established intervals. An interpretation of oFFA tutorial was delivered to consultant ophthalmologists and trainees. Subsequently, these groups were assessed using a series of fifteen cases with the sensitivity and specificity of the test determined. RESULTS: Our study presents a series of images and descriptions for common optic nerve abnormalities in paediatric populations. In the interpretation part of the study, overall sensitivity of 76.8% in the consultant group vs 63.3% in the combined consultant + trainees and specificity of 87.5% vs 68.4% in the combined group. CONCLUSIONS: This is the first study that describes characteristic features of several common, and serious, optic nerve abnormalities specifically for oFFA interpretation in a paediatric population. It also highlights the rapid accumulation of oFFA interpretation skills in non-specialist consultant and trainee ophthalmologists such as to obtain a high diagnostic accuracy with high sensitivity and specificity.

VKH disease in the elderly: Variations in clinical course as compared to VKH disease in adults.

PURPOSE: To describe disease characteristics and outcomes of Vogt-Koyanagi-Harada (VKH) disease in elderly patients. METHODS: Retrospective analysis of patients older than 50 years with VKH disease at two referral centers in India. Demographics, extraocular and ocular involvement, treatment, complications, and visual acuity outcomes were noted. RESULTS: In total, 69 patients (mean age at presentation: 56.4 ± 4.7 years) were analyzed; 6/69 patients had diabetes mellitus at presentation, and 10/69 had hypertension. Clinical signs included anterior chamber cells >2+ (29%), granulomatous keratic precipitates (23%), disc hyperemia (26%), neurosensory retinal detachment (34.7%), and "sunset-glow" fundus (52.1%). Patients were classified as probable (n = 50, 72.4%), incomplete (n = 18, 26%), and complete VKH (n = 1, 1.4%). The mean follow-up period was 20.2 ± 19.4 months. Improvement in mean BCVA of (0.63 LogMAR, 6 Snellen lines) was noted on the last follow-up. Patients receiving systemic steroids with immunosuppressants ( P < 0.0001) had better visual outcomes at final follow-up compared to steroids alone ( P = 0.103). Eight patients (11.6%) had complications due to systemic immunosuppressants, and 17 patients (24.6%) developed diabetes mellitus or had worsening of diabetes while on systemic corticosteroids. CONCLUSION: Few patients presented with systemic manifestations in our cohort. Those treated with steroids and concurrent immunosuppressants had better outcomes. However, therapy with immunosuppressants was encountered with major dose-limiting complications in a significant number of elderly patients with VKH syndrome.

LV Prasad Eye Institute EyeSmart electronic medical record-based analytics of big data: LEAD-Uveitis Report 1: Demographics and clinical features of uveitis in a multi-tier hospital based network in Southern India.

Purpose: To describe the demographics and epidemiology of uveitis presenting to a multi-tier ophthalmology hospital network in Southern India. Methods: Cross-sectional hospital-based study of 19,352 patients with uveitis presenting between March 2012 and August 2018. Results: In total, 1,734,272 new patients were seen across the secondary and tertiary centers of our multi-tier ophthalmology hospital network during the study period. Among them, 25,353 eyes of 19,352 patients were diagnosed with uveitis and were included in the study. Uveitis constituted 1.11% of all cases. The majority of patients were male (60.33%) and had unilateral (68.09%) affliction. The most common age group was 21-50 years with 12,204 (63.06%) patients. The most common type of uveitis was anterior uveitis, which was seen in 7380 (38.14%) patients, followed by posterior uveitis in 5397 (23.89%) patients. Among the infectious causes, tuberculosis was the most common etiology (2551 patients, 13%) followed by toxoplasmosis (1147 patients, 6%). Conclusion: Uveitis constituted 1.11% of all cases presenting to our clinics. It was more common in the age group of 21-50 and was predominantly unilateral. Anterior uveitis was the most common subtype seen in 38%.

Vogt Koyanagi Harada Disease In Paediatric Age Group: Clinical Characteristics, Remission, Recurrences and Complications in Asian Indian Population.

PURPOSE: To describe disease characteristics and outcomes of Vogt-Koyanagi-Harada (VKH) syndrome in paediatric patients. STUDY DESIGN: Retrospective chart analysis. METHODS: A RETROSPECTIVE: Analysis of all patients ≤16 years with VKH syndrome was done. Clinical presentations, complications, recurrences and outcomes in cases of paediatric VKH were reviewed. RESULTS: 72 eyes of 36 patients with a mean age at presentation of 13.7 ± 2.34 years were assessed. Mean duration of symptoms and follow up were 9.88 ± 17.3 weeks and 55 months respectively. Clinical signs at presentation included anterior chamber cells >2+(34/72eyes, 47.2%), granulomatous keratic precipitates (6 eyes, 8.3%), posterior synechiae (35 eyes,48.6%), disc edema (46 eyes, 63.8%), neurosensory retinal detachments (44 eyes, 61.1%) and 'sunset-glow' fundus (9 eyes, 12.5%). Best corrected visual acuity (BCVA) at the time of presentation was 1.3logMAR or a Snellens equivalent of 20/400 which improved to 0.51logMAR (Snellens equivalent of 20/63) at last follow up. Remission was achieved in 61.1% cases. More than half of our patients developed one or more complications. CONCLUSION: VKH in paediatric patients poses a challenge due to a delayed presentation and paediatric VKH patients have a worse visual acuity at the time of presentation as compared to adult age groups. Rates of remission may be low along with high risk of complications and hence there is a need for prolonged immunosuppression.

Sight-threatening intraocular infection in patients with COVID-19 in India.

PURPOSE: Intraocular infection in patients with COVID-19 could be different in the presence of treatment with systemic corticosteroid and immunosuppressive agents. We describe the epidemiology and microbiological profile of intraocular infection in COVID-19 patients after their release from the hospital. METHODS: We analyzed the clinical and microbiological data of laboratory-confirmed COVID-19 patients from April 2020 to January 2021 presenting with features of endogenous endophthalmitis within 12 weeks of their discharge from the hospital in two neighboring states in South India. The data included demography, systemic comorbidities, COVID-19 treatment details, time interval to visual symptoms, the microbiology of systemic and ocular findings, ophthalmic management, and outcomes. RESULTS: The mean age of 24 patients (33 eyes) was 53.6 ± 13.5 (range: 5-72) years; 17 (70.83%) patients were male. Twenty-two (91.6%) patients had systemic comorbidities, and the median period of hospitalization for COVID-19 treatment was 14.5 ± 0.7 (range: 7-63) days. Infection was bilateral in nine patients. COVID-19 treatment included broad-spectrum systemic antibiotics (all), antiviral drugs (22, 91.66% of patients), systemic corticosteroid (21, 87.5% of patients), supplemental oxygen (18, 75% of patients), low molecular weight heparin (17, 70.8% of patients), admission in intensive care units (16, 66.6% of patients), and interleukin-6 inhibitor (tocilizumab) (14, 58.3% of patients). Five (20.8%) patients died of COVID-19-related complications during treatment for endophthalmitis; one eye progressed to pan ophthalmitis and orbital cellulitis; eight eyes regained vision >20/400. Fourteen of 19 (73.7%) vitreous biopsies were microbiologically positive (culture, PCR, and microscopy), and the majority (11 patients, 78.5%) were fungi. CONCLUSION: Intraocular infection in COVID-19 patients is predominantly caused by fungi. We suggest a routine eye examination be included as a standard of care of COVID-19.

Subfoveal retinal pigment epithelium inflammatory lesion presenting as a sign of reactivation of tubercular multifocal choroiditis.

Multifocal choroiditis (MFC) can be associated with ocular tuberculosis (TB). Inflammatory peripapillary choroidal neovascular membrane (PPCNVM) is uncommon in TB MFC. Subretinal pigment epithelial inflammatory lesions are suggestive of acute inflammation or reactivation of inflammation in the setting of MFC. We present a case of MFC, of tubercular aetiology, during course of treatment of PPCNVM developed a subfoveal retinal pigment epithelial lesion. Clinical examination suggested a recurrence of PPCNVM, with the new macular lesions posing a dilemma of new onset inflammatory choroidal neovascular membrane (CNVM) at the macula versus reactivation of choroiditis at the posterior pole. Multimodal imaging helped differentiate the lesion from CNVM and give the appropriate antitubercular treatment to prevent future recurrences.

Recent Advances in Diagnosis and Treatment of Infectious Uveitis Prevalent in Asia-Pacific Region.

ABSTRACT: The role of infections in intraocular inflammation is being increasingly recognized across the world. The Asia-Pacific region, being the single largest and most populous geographical entity on the planet, is home to a wide variety of such infections. Not surprisingly, there has been an explosion in the literature on infectious uveitis emerging from Asia-Pacific countries. In this review, we have covered recent advances in the diagnosis, treatment, and pathogenesis of common forms of infectious uveitis from the Asia-Pacific region. Much of the literature is focussed on the diagnosis of these infections by clinical criteria and laboratory investigations. There has also been an increased emphasis on the application of newer modes of ocular imaging and understanding pathomechanisms of ocular inflammation in these infections. Together this research has significantly improved our understanding of the diagnosis and management of infectious uveitis.

Miliary Retinal Lesions in Ocular Syphilis: Imaging Characteristics and Outcomes.

Purpose: To describe full thickness miliary retinal lesions in ocular syphilis.Methods: Retrospective chart review of patients with serologically confirmed ocular syphilis. Retinal miliary lesions in three cases of Syphilitic uveitis, in immunocompetent individuals are described. Case 1 and case 2 were positive for both VDRL (venereal disease research laboratory) and TPHA (Treponema pallidum hemagglutination), case 3 was VDRL negative but TPHA positive.Results: Miliary lesions were small round to oval, yellow retinal lesions, measuring less than » disc diameter size, with distinct margins, involving complete thickness of retina on OCT, in a pillar like manner, associated with ground glass retinitis, outer retinal placoid lesion or with retinal vasculitis. In cases 1 and 3, these healed with pigmentation.Conclusion: In contrast to similar lesions described, retinal miliary lesions seem to involve full thickness of the retina on OCT and may heal with pigmentation. These lesions may be characteristic of ocular syphilis.

CLINICAL PREDICTORS OF TUBERCULAR RETINAL VASCULITIS IN A HIGH-ENDEMIC COUNTRY.

PURPOSE: To determine clinical signs suggestive of tubercular etiology in retinal vasculitis. METHODS: A retrospective comparative study of patients who presented with retinal vasculitis at three tertiary care centers in India. All patients underwent detailed clinical evaluation and tailored laboratory investigations for etiological diagnosis. Tubercular etiology was diagnosed on basis on the presence of retinal periphlebitis in association with ancillary evidence of systemic tuberculosis and exclusion of nontuberculosis entities. Patients with tubercular (Group A) and nontubercular (Group B) etiology were compared for demographic characteristics, supportive diagnostic evidence, and specific ocular signs. Statistical analysis was performed at 5% confidence levels. RESULTS: Of the 114 patients diagnosed with retinal vasculitis, Group A had 69 patients (100 eyes) and Group B had 45 patients (75 eyes). Active or healed subvascular lesions (P ≤ 0.0001), focal vascular tortuosity (P ≤ 0.0001), and occlusive vasculitis (P = 0.002) were significantly more common in Group A patients than in Group B patients. All three were independent predictors of tubercular etiology on multivariate regression analysis. CONCLUSION: The presence of healed or active subvascular lesions, focal vascular tortuosity, and occlusive vasculitis could be predictive of tubercular etiology in retinal vasculitis.

Increased local expression of P-glycoprotein on CD4+ T-cells in vitreous of patients with non-infectious uveitis: a pilot study.

Nearly a third of uveitis patients are unable to achieve adequate inflammation control with conventional anti-inflammatory therapy. Several factors are known to influence responsiveness to anti-inflammatory therapy. In this pilot study, we have investigated the local expression of P-glycoprotein, an efflux-transport protein with role in multi-drug resistance, in vitreous CD4+ T-cells of patients with non-infectious uveitis (NIU). CD4+ T-cells were isolated from vitreous and peripheral venous blood samples of NIU patients undergoing therapeutic vitrectomy. Rhodamine-123, a substrate of P-glycoprotein, whose retention inside cells is inversely proportional to P-glycoprotein function, was used to assay this transporter protein. In addition, cells were stained with IFN-γ, IL-17, GM-CSF and FoxP3, and analysed by flow cytometry. T-cell mitochondria were imaged by Mitotracker Red and confocal microscopy. Vitreous CD4+ T-cells expressed significantly higher P-gp and pro-inflammatory (IL-17+, IFNγ+IL17+) cytokine expression than matching blood samples. Mitochondrial fission was noted in vitreous T-cells and fusion in blood. We concluded that NIU is associated with higher P-glycoprotein expression and pro-inflammatory state in vitreous than in blood. This supports P-glycoprotein inhibition and adjunctive local anti-inflammatory treatment in management of NIU.

Extraocular spread following evisceration for rapidly progressive intraocular tuberculosis.

We describe a case of right eye tubercular (TB) panuveitis with corneal involvement where repeated intraocular sampling was unsuccessful. Finally, evisceration and histopathology of ocular tissue confirmed the diagnosis of ocular tuberculosis. A chest X-ray showed signs of pulmonary TB. The patient was lost to follow-up but reported 2 months later with the right eyelid margin nodules with surface ulceration. Both eyelid and pulmonary lesions were resolved with anti-TB therapy.

Role of Multidrug Resistance Proteins in Nonresponders to Immunomodulatory Therapy for Noninfectious Uveitis.

Purpose: Nearly a third to half of patients with noninfectious uveitis (NIU) fail to achieve control with immunomodulatory therapy (IMT). Multidrug resistance (MDR) proteins are transmembrane proteins that allow efflux of intracellular drugs, leading to drug resistance. The aim of our study was to compare MDR protein function in blood CD4+ cells between responders and nonresponders to IMT. Methods: We included NIU patients on IMT for ≥6 months and corticosteroid dose ≤10 mg/d. Nonresponders to treatment were those with worsening (two or more steps) of inflammation in the past 3 months on full-dose immunosuppressive therapy. MDR function was assessed by Rhodamine-123 dye retention in blood CD4+ cells. Three nonresponders were treated with adjunctive oral cyclosporine A (CSA, MDR inhibitor) therapy for 2 months and reevaluated. Results: Fourteen NIU patients were recruited. Most (n = 8) had Vogt-Koyanagi-Harada disease. These included nine nonresponders and five responders to IMT. Nonresponders produced significantly higher MDR function and proinflammatory cytokines (interferon γ, tumor necrosis factor α, interleukin 17, and Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)) than responders. In vitro CSA treatment of CD4+ cells inhibited MDR expression and proinflammatory cytokine production while increasing Foxp3. Finally, adjunctive oral CSA therapy led to improvement in clinical inflammatory scores with a concurrent decrease in MDR function and proinflammatory cytokine secretion. Conclusions: MDR function is significantly higher in CD4+ T cells of nonresponders to IMT. Adjunctive CSA therapy may decrease MDR function and allow improvement in treatment response to IMT. Translational Relevance: Our study highlights the need for MDR inhibition strategies in NIU patients not responding to IMT for improving the efficacy of anti-inflammatory therapy.

Clinical manifestations and outcomes of ocular syphilis in Asian Indian population: Analysis of cases presenting to a tertiary referral center.

PURPOSE: To describe disease manifestations and outcomes of ocular syphilis in Asian Indian population. METHODS: Retrospective analysis of patients diagnosed with ocular syphilis at a tertiary referral center in India. Demographics, history, extraocular and ocular manifestations, ocular and systemic investigations, treatment and visual acuity outcomes were noted. All patients were diagnosed after necessary laboratory investigations including HIV ELISA (Human immunodeficiency virus, enzyme-linked immunosorbent assay), VDRL (venereal disease research laboratory), and TPHA (treponema pallidum hemagglutination). RESULTS: Totally, 20 patients with mean age at presentation 38.25 ± 9.76 were analyzed. 9/20 patients had bilateral involvement. 8/20 had concurrent HIV at presentation with an average CD4 counts of 592.25 ± 411.34 cells/microliter. The mean duration of symptoms at time of presentation was 15.45 ± 35.15 weeks. VDRL test was reactive in 45% (9/20) patients whereas, all patients had a reactive TPHA test. Clinical manifestations included outer retinal placoid chorioretinitis lesions (8/20, 40%), followed by retinitis mimicking acute retinal necrosis as the second most common phenotype (4/20, 20%). Other presenting manifestations noted were panuveitis, miliary retinitis lesions, retinal vasculitis, intermediate uveitis, and anterior uveitis. The clinical phenotypes in immunocompromised included panuveitis, acute retinal necrosis and isolated anterior uveitis. Mean follow up duration was 6.32 ± 6.15 months. An improvement in mean best corrected visual acuity (BCVA) of (0.63 LogMAR, approximately 6 Snellen lines, P < 0.02) was noted at last follow-up. CONCLUSION: Phenotypic manifestations of ocular syphilis are varied. Non-treponemal tests like VDRL may be unreliable when compared with treponemal tests in diagnosing ocular syphilis. Syphilitic uveitis is considered equivalent to neurosyphilis and is treated similar to neurosyphilis.

Syphilitic chorioretinitis presenting as a choroidal granuloma.

A rare case of syphilitic uveitis presenting as a choroidal granuloma is described in this case report. The clinical picture resembled that of a tubercular choroidal granuloma. However, the patient was positive for treponemal (treponema pallidum hemagglutination assay) as well as non-treponemal tests (venereal disease research laboratory test) for syphilis. Therefore, the patient was treated for ocular syphilis and responded to antisyphilitic therapy. There was a complete resolution of the lesion at the end of 14 days of treatment.

Small cell neuroendocrine carcinoma of the orbit presenting as an orbital abscess in a young female.

Small cell neuroendocrine carcinoma (SNEC) of the sino-nasal tract is a rare tumor with aggressive behavior. Invasion of the orbit, brain and base of skull is reported in advanced cases, however clinical presentation of SNEC, primarily as an orbital mass is distinctly rare. A 25-year-old female, presented to a local ophthalmologist with sudden protrusion of eyeball and was diagnosed as an orbital abscess which was incised and drained. She presented to us after six months of initial drainage with rapid increase in protrusion and associated eyelid swelling and was lactating at the time of presentation. The patient underwent clinico-pathological work up and was diagnosed as a primary case of orbital SNEC. She received chemotherapy, with an initial response followed by massive recurrence and subsequently succumbed to the disease after 18 months of presentation to us. The authors present a literature review and describe the challenges in diagnosis and management of a primary orbital SNEC, which has high propensity to progress, recur, invade neighboring sites, and show distant metastasis inspite of multimodal therapy. Author's recommend close follow up during disease free intervals.

Role of PASCAL and optical coherence tomography angiograpgy in the treatment of diffuse unilateral subacute neuroretinitis caused by large live motile worm.

A 46-year-old male presented with best corrected visual acuity (BCVA) of 20/125 in his right eye. Fundus showed disc edema, multiple yellow outer retinal crops, macular edema and a live motile worm in the subretinal space. Diagnosis of diffuse unilateral subacute neuroretinitis (DUSN) was made and pattern scanning laser photocoagulation (PSLP) was performed along with administration of oral albendazole, diethylcarbamazine and corticosteroids. Complete disappearance of the worm was observed at 2 weeks. At last follow up, final BCVA improved to 20/30. Herein, we report role of PSLP in the management of DUSN.