Extraocular Disease Research Articles

Punctal Atresia As a Clinical Indicator of Systemic Genetic Anomalies

ABSTRACT Background Punctal atresia or agenesis (PA) is a rare congenital anomaly characterized by the absence or closure of the tear duct puncta, potentially linked to systemic genetic anomalies. The necessity of a genetic workup based solely on the presence of PA remains uncertain. This study investigates a cohort of PA patients, examining the prevalence and types of associated syndromes. Methods A retrospective medical records review of all patients diagnosed with PA at the Children’s Hospital of Philadelphia between 2009–2023 was conducted, analyzing medical histories and genetic testing results. Primary outcomes included the prevalence of systemic syndromes, while secondary outcomes focused on the variety of associated syndromes. Results Forty-four patients were included, of which 31 were male (70%) with a mean ± SD age 3.3 ± 3.3 years. Overall, 87 puncta in the study cohort were affected, and 26 cases (59%) were bilateral. Systemic abnormalities or genetic syndromes were identified in 19 patients (43%), with the most common being Ectodermal Dysplasia and Down syndrome. Additional rare syndromes were demonstrated. No significant association was found between systemic abnormalities and gender, bilaterality, or the number of puncta involved. Conclusions A high incidence of systemic syndromes (43%) was observed in the study cohort. In individuals with PA who also exhibit extraocular disease, systemic evaluation and genetic workup should be considered. Syndromic diagnoses identified in our cohort also include: Branchio-oto-renal syndrome, 22q11.2 deletion syndrome, 1q21.1 microdeletion syndrome, NF1, monosomy 4q and trisomy 6q, which represent novel associations. The lack of correlation between PA’s phenotypic severity and systemic abnormalities highlights the need to obtain a comprehensive medical history and consider a systemic workup in PA patients.

Retinoblastoma treatment in a Brazilian population. Presentation and long-term results.

Retinoblastoma is a malignant tumor with a high cure potential when proper therapy is used. The purpose of this paper is to report the clinical features and outcomes of patients with retinoblastoma who were treated with a combination of local and systemic chemotherapy-based protocols. We retrospectively studied patients treated with systemic chemotherapy plus local treatment between 2003 and 2015 with a follow-up ≥2 years. We correlated clinical and pathological characteristics with decimal visual acuity (VA) and death. Among 119 patients, 60% had unilateral disease (UNI), and 52% were male. The median presentation age was 19.5 months, 10% had a positive family history, and the most frequent sign was leukocoria (68.8%). Advanced disease was more frequent in eyes with UNI (98.4%) than in eyes with bilateral retinoblastoma (BIL: 55.3%). Enucleation was performed in 97% of UNI eyes and in 55.8% of BIL eyes. The overall globe salvage was 26.6%, 44.25% of BIL eyes. Bilateral enucleation was required in 5%. High-risk pathologic features occurred in 50% and 37% of eyes enucleated without and with neoadjuvant chemotherapy, respectively. High-risk features were related to the presence of goniosynechiae in the pathologic specimen and were more frequent in children younger than 10 months or older than 40 months. Extraocular disease was present in 5% of patients, and the death rate related to metastasis of the tumor was 8%. The final VA was ≥ 0.7 in 72.8% and ≥0.1 in 91% of BIL patients. Treatment of retinoblastoma with conservative systemic-based chemotherapy was associated with an excellent survival rate (92%). Albeit the low overall globe salvage rate, in BIL patients, approximately half the eyes were conserved, and a satisfactory functional visual result was achieved The evaluated protocol is an important treatment option, especially in developing countries.

Philippine retinoblastoma initiative multi-eye center study 2010-2020.

To provide a comprehensive and more representative national data on the disease, especially on treatment options and outcomes, and to determine access of retinoblastoma patients from Luzon, Visayas and Mindanao to eye care, and determine if access is associated with delay in consultation, staging and outcomes. Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon, Vizayas and Mindanao from 2010-2020. Totally 636 patients, involving 821 eyes, were included. Majority (57%) were from Luzon and were seen in institutions in Luzon (72%). Annually, 58±10 new cases were seen with 71% having unilateral disease. Median delay of consultation remained long at 9 (3, 17)mo, longest in patients with unilateral disease (P<0.02) and those from the Visayas (P<0.003). Based on the International Retinoblastoma Staging System, only 35% of patients had Stage 1 while 47% already had extraocular disease. Enucleation was the most common treatment received by 484 patients while intravenous chemotherapy was received by 469. There were 250 (39%) patients alive, 195 (31%) dead, 85 (13%) abandoned, 17 (3%) refused and 89 (14%) with no data. This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients' and participating institutions' number and geographical location and type of institution (private and public). It also presents more comprehensive data on the treatments used and outcomes (survival, globe salvage, and vision retention rates). Delay in consultation was still long among patients leading to advanced disease stage and lower survival rate. Despite increasing capacity to diagnose and manage retinoblastoma in the country, the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial concerns. The delay was still significant that overall survival rate remain low.

Outcomes of Children Diagnosed with Unilateral Retinoblastoma: Retrospective Audit

To evaluate treatment outcomes of children diagnosed with unilateral retinoblastoma. Retrospective study of children diagnosed with unilateral retinoblastoma registered at the Tata Memorial Hospital (TMH), Mumbai from January 2013 to December 2018 and completed the planned curative treatment protocol. For the 98 cases that were analyzed, the median age of presentation was 24 months. The majority of patients had the intraocular disease (n = 72), whereas orbital retinoblastoma was in 26 patients. At the time of presentation, on imaging extra scleral spread was observed in 16 patients whereas 18 patients had optic nerve involvement, 11 patients had both extra scleral invasion and optic nerve involvement. We used the International Classification of Retinoblastoma for grouping. Out of 98 patients, 71 patients were in Group E, 21 were in Group D and 4 were in Group B and 2 were in Group C. For Staging of Retinoblastoma, we used International Retinoblastoma Staging System (IRSS) in our study and 14 patients had Stage 0 disease, 52 patients had Stage I disease, 10 patients had Stage II, 21 patients had Stage III A and 1 patient had Stage III B disease. High-risk features on surgical specimen histopathology were optic nerve cut margin positive in 6 patients, optic nerve involvement in 21 patients, extra scleral spread in 3 patients, Choroidal invasion in 38 and Iris involvement in 10 patients. Primary enucleation was offered in 52 patients whereas 26 patients underwent secondary enucleation. Systemic chemotherapy was received by the patient in the neoadjuvant setting in 17 patients as a form of chemo-reduction and 51 patients received systemic chemotherapy in the adjuvant setting. Intra-arterial chemotherapy was offered to 27 patients as a primary treatment or in conjugation with focal therapy (n = 11). Definitive radiotherapy was offered to only 2 patients and 22 patients received adjuvant radiotherapy. At a median follow-up of 62 months, 2patients had local relapse, which was salvaged by focal therapy in one and enucleation in the other. Ten patients who had leptomeningeal relapse had died. The 5-year local control (LC) is 97.6%, event-free survival (EFS) is 88% and overall survival (OS) is 89.5%. Globe was salvaged in only 16 cases. On univariate analysis, we observed a significant association between overall survival and extraocular and intraocular disease (p-value 0.0), Extra scleral spread (p-value 0.0), optic Nerve involvement (imaging), and an optic nerve cut margin positive (p-value 0.045), ICRB Groups (p-value 0.0) and IRSS stage (p- value 0.024). Retinoblastoma is curable if detected early. Extra ocular disease and high-risk features are associated with inferior outcomes and poor globe salvage rates.

Causes of death and survival analysis for patients with retinoblastoma in Jordan.

To analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan. We reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death. Twenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4-38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms (n = 3) or metastases (n = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage (p < 0.0001), the presence of high-risk pathological features in the enucleated eyes (p = 0.013), parental refusal of the recommended primary treatment plan (p < 0.0001), and extraocular extension (p < 0.0001). The 5-year survival rates of Rb patients in Jordan are as high as those in high-income countries. However, 5% are still dying from metastatic disease, prompting the need for awareness campaigns to educate the public about the high cure rates and to prevent treatment abandonment.

Adjuvant Chemotherapy Improves Survival for Children With Massive Choroidal Invasion of Retinoblastoma.

The purpose of this study was to investigate the effect of adjuvant chemotherapy on outcomes of children with massive choroidal invasion (MCI). In this study, we reviewed the 5-year relapse-free survival (RFS) and overall survival (OS) of children diagnosed with MCI, managed with or without adjuvant chemotherapy. Excluded were children with additional other high-risk features (post-laminar optic nerve invasion, scleral invasion, or overt extraocular disease). Of 3566 children diagnosed with retinoblastoma, 2023 had enucleation, and 60eyes of 60 children had pathology showing MCI without concomitant high-risk features. Enucleation was primary (22, 37%), or secondary (38, 63%) after failed eye salvage. Adjuvant systemic chemotherapy (median = 4, range = 1-8 cycles) was given to 48 of 60 (80%) children; 12 of 60 (20%) children had no adjuvant therapy. Five-year RFS was 88.5% (95% confidence interval [CI] = 79.7%-97.3%) and 5-year OS was 90.1% (95% CI = 81.7%-98.5%). Pre-enucleation chemotherapy did not affect RFS (89.7% vs. 75.0%; P = 0.657). Adjuvant chemotherapy improved RFS (97.2% vs. 55.6%; P < 0.001) and OS (97.2% vs. 66.7%; P < 0.001). In subgroup analysis, adjuvant chemotherapy improved RFS for both primarily enucleated (5-year RFS 100% vs. 50.0%; P = 0.002) and secondarily enucleated children (5-year RFS 95.8% vs. 60.0%; P = 0.005). The number of children treated with adjuvant chemotherapy to prevent one post-enucleation systemic relapse or death is three. Adjuvant chemotherapy significantly decreased the risk of tumor relapse and death for children with pathological MCI. For every three children treated with adjuvant chemotherapy, one systemic relapse or death could be prevented.

Herpes simplex virus dissemination with necrotizing hepatitis following Descemet membrane endothelial keratoplasty

BackgroundCorneal transplants are the most common type of transplant and increasing in frequency. Donor cornea tissues are a rare source of herpes simplex virus (HSV) transmission and not routinely tested for presence of HSV. Donor graft-to-recipient transmission typically causes graft failure and anterior uveitis, and extra-ocular HSV disease has not been previously reported. We present a case of HSV transmission from donor cornea tissue that nearly cost the corneal transplant recipient his life.Case reportAn elderly immunocompetent man developed an acute illness 10 days after having donor corneal tissue implanted in a Descemet membrane endothelial keratoplasty (DMEK). He was found to have HSV necrotizing hepatitis per liver biopsy, trilineage cytopenia, rhabdomyolysis, acute kidney failure, altered mental status, early-stage hemophagocytic lymphohistiocytosis (HLH), and donor corneal tissue implant infection resulting in graft failure and anterior uveitis. HSV DNA was detected in cerebral spinal fluid, peripheral blood, explanted donor corneal tissue, and anterior chamber fluid (220 million HSV DNA copies per mL). HSV-1 seroconversion denoted a primary HSV infection, and the patient had no other risk factor for HSV acquisition. Early recognition of HSV dissemination prompting treatment with intravenous acyclovir, as well as a short course of HLH-directed therapy, resolved the systemic illness. Vision was restored to near normal by replacement of the infected corneal graft with new donor DMEK tissue in conjunction with intravitreal foscarnet treatment.ConclusionAwareness of the potential risk of donor cornea tissue transmitting HSV and leading to life-threatening HSV disease is paramount to early diagnosis and treatment. The role of donor cornea tissue in HSV transmission and disease merits additional attention and investigation.

Clinical features and outcome of retinoblastoma at the Vietnam National Cancer Hospital.

To characterize the clinical features, treatment, and outcome of children diagnosed with retinoblastoma (RB) at Vietnam National Cancer Hospital. The study enrolled all RB patients newly diagnosed at Vietnam National Cancer Hospital from January 2018 to December 2022. The primary endpoint was overall survival (OS) and the eye salvage rate. In total, 139 patients were enrolled, 51.8% patients were male. Median age was 18.9months. Most patients presented with leukocoria (63.3%), followed by strabismus (14.4%), and 43.9% had bilateral disease. Of 200 eyes, 129 (64.5%) were classified as group E. Extraocular extension was noted in 10 of 139 patients (7.2%). About one-third of the patients lived more than 300 kilometers (km) away from these hospitals, and 17.3% of the patients belonged to minority groups, both of which were dominated by group E and extraocular or high-risk eyes at the time of consultation. Primary enucleation was done for 57 eyes (28.5%), and 51 of 61 patients (83.6%) received eye salvage therapy in bilateral RB group. At study closure, 127 children were alive at the last follow-up, 12 cases were confirmed dead. The 5-year OS and progression-free survival (PFS) rates were 90.3% and 85.9%, respectively. In particular, ethnic minority, distance to hospital more than 150km, and extraocular disease were significantly associated with higher mortality among children with RB treated in Vietnam National Cancer Hospital. There is a need to support for screening RB with early symptoms in grassroots medical facilities and raise awareness among patients' families through health education programs. Besides, caring and supporting treatment for patients from the ethnic minority and who live far from hospitals are also extremely necessary.

Toxicity and feasibility of vincristine, etoposide, and carboplatin alternating with vincristine, doxorubicin, and cyclophosphamide in children with advanced retinoblastoma in Guatemala.

Retinoblastoma is highly curable, with event-free survival (EFS) of greater than 95% in high-income countries. However, in lower middle-income countries, outcomes of EFS are 30%-60% due to delayed diagnosis and lack of resources resulting in extra-ocular disease. We report the toxicity profile and outcomes of intensified therapy for advanced retinoblastoma: vincristine, etoposide, carboplatin (VEC) alternating with vincristine, doxorubicin, and cyclophosphamide (VDoCx) in Guatemala. Compared to VEC alone, similar rates of neutropenia, anemia, and thrombocytopenia were seen, with no toxic deaths. Although survival was not a primary objective, a modest survival benefit supports further investigation of VEC+VDoCx for advanced retinoblastoma.

Late ophthalmologic manifestations of monkeypox in a Latin American immunosuppressed patient.

The re-emergence of Monkeypox (MPX) and its related ophthalmic disease represent a clinical challenge in the initial stages because of the presence of lesions like those caused by varicella zoster, syphilis, and other infections due to other poxviruses. Human Immunodeficiency Virus (HIV) infection and secondary immunodepression raise the risk of severe and prolonged disease. We present the case of a young immunosuppressed male patient with MPX, who presented with multiple skin lesions, also including risky ophthalmological manifestations due to extensive eyelid involvement. We describe a novel form of late-onset conjunctivitis and eyelid lesions, without active extraocular disease, highlighting the heterogeneous behavior of the new clinical form of MPX, that exhibits a wide spectrum of lesions in different stages of evolution.

Cytomegalovirus retinitis in hospitalized people living with HIV in the late antiretroviral therapy era in São Paulo, Brazil.

There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features. This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/μL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation. Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma. These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.

OCULAR MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS – A CLINICAL STUDY

Aim: To determine the various ocular manifestations of SLE for early diagnosis, prompt initiation of therapy and better prognosis of SLE cases. A total of 50 diagnosed patients of SLE attending RIO a Materials And Methods: nd department of Dermatology, GMCH were selected for the study. Detailed history and a thorough ocular examination was performed. Laboratory investigations including R/E blood, ESR, RBS, R/E urine, 24 hours urinary protein, RFT and ANA were done. Results And Observations: Incidence of ocular manifestations of SLE was 70%. The mean age of presentation was 32.2 years. The female: male was 11.5:1. The median duration of illness was 1.75 years. The commonest systemic involvement was hematological(90%), followed by cutaneous(64%), musculoskeletal(60%), renal(42%), serosal(4%), neurological(2%). 72% had SLEDAI score ≤10 and 28% had &gt;10. Anterior segment involvement(58%) is more than posterior segment(12%). Common anterior segment manifestations were Keratoconjunctivitis sicca, PSC, eyelid lesions, ulcerative blepheritis, subconjunctival haemorrhage, periorbital oedema, PUK, episcleritis. Posterior segment manifestations were lupus retinopathy, hypertensive retinopathy, CSCR, CRVO, optic atrophy and pigmentary maculopathy. 56% were on steroid therapy, 36% were on steroid+HCQS and 8% were on steroid+cyclophosphamide. SLE is a multisyst Conclusion: em disease with varied manifestations and diagnosis depends upon careful evaluation of all the systems including the eye. The ophthalmologist may play an important role in the care of the SLE patients, since ocular inammatory lesions may precede potentially serious extraocular disease and may guide towards the diagnosis.

Retinal Artery Occlusion as an Early Indicator of Macrovascular Complications in Diabetes

BackgroundA characteristic of the retinal circulation is that arterial occlusion is embolic or secondary to vasculitis but rarely or never due to in situ atherosclerosis. Therefore, retinal artery occlusion suggests the presence of cardiac or large-vessel disease outside the eye. This cohort study examined the general risk of macrovascular disease in individuals with diabetes, with or without retinal artery occlusion. MethodsWe retrieved data on 992 subjects with incident retinal artery occlusion and preexisting diabetes, registered in Denmark between January 1, 2000, and December 31, 2018. Each retinal artery occlusion subject was matched for age, sex, and diabetes duration, with 5 control subjects with diabetes but without retinal artery occlusion. We performed survival analyses to compare the risk of extraocular macrovascular disease between the 2 groups in a 5-year follow-up. ResultsAfter 1 year, the incidence of macrovascular disease in subjects with retinal artery occlusion was approximately 21 per 100 person-years (95% confidence interval [CI]: 18.11-24.29), compared to 6.25 per 100 patient-years (95% CI: 5.57-7.00) in those without retinal artery occlusion. After 5 years, the cumulative incidences of macrovascular disease were 51.2% (95% CI: 47.9-54.7%) and 29.4% (95% CI: 28.0-30.8%) in patients with diabetes with or without retinal artery occlusion, respectively. Hazard rate ratios were 3.36 (95% CI: 2.79-4.05) after 1 year and 2.27 (95% CI: 2.04-2.53) after 5 years. ConclusionAmong individuals with diabetes, those diagnosed with retinal artery occlusion had a higher general risk of macrovascular complications for at least 5 years after the occlusion event compared with those without retinal artery occlusion.

Expression of Ki67 as detected by MIB-1 and its association with histopathological high-risk factors among patients with retinoblastoma tumour: a cross-sectional study

ObjectivesThis study aims to investigate the expression of Ki67 in formalin-fixed paraffin-embedded tissue blocks from patients with a diagnosis of retinoblastoma tumour (RbT) as well as determining its association with...

The Role of Bone Marrow in Baseline Investigations for Advanced Intraocular Retinoblastoma

Objective: To assess the rationale for bone marrow biopsy/aspiration as a part of a routine systemic workup in advanced intraocular retinoblastoma (RB) in relation to high-risk histopathological post-enucleation features. Methods: A retrospective observational study was conducted at the Department of Pediatric Hematology and Oncology of the Children’s Hospital, Lahore, Pakistan. Data regarding demographics, clinical presentations, staging workup, and treatment strategies of all the newly diagnosed retinoblastoma cases registered at our centre from January 2018 to December 2019 were collected. Statistical analysis was performed using IBM SPSS statistics version 22. Results: Of the 61 patients, 41 (67%) showed unilateral disease, while bilateral and trilateral involvement was found in 17 (28%) and three (5%) cases, respectively. The mean age of presentation in our cohort was 25 months (median: 24 months; range: &lt;1–72 months). Amongst 81 eyes (61 patients), tumours were limited to an intraocular location in 54 eyes (46 patients). In this group, 42 eyes (38 patients) underwent enucleation. Adverse histopathology was found only in nine (23.68%) patients. None of the patients with the intraocular disease, with or without adverse histopathological features in enucleated eyes, were found to have bone marrow (BM) involvement. For 15 patients with extraocular disease, five (33%) patients were found to have bone marrow involvement based on initial investigations. Conclusion: Our study did not show any correlation between bone marrow positivity and advanced intraocular groups D/E RB. Therefore, BM evaluation can be avoided in this subset of patients with retinoblastoma at presentation, while stage III and IV patients (International Retinoblastoma Staging System IRSS) must be evaluated for metastasis. This will reduce the risks of biopsy to the patients and the burden on services. Keywords: Retinoblastoma, Bone Marrow Involvement, Intraocular disease.

Ocular Mucus Membrane Pemphigoid: A Primary Versus Secondary Entity.

The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens-Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up. Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.

Utility of Direct Immunofluorescence Using Buccal Mucosal Biopsies in Those with Suspected Isolated Ocular Mucous Membrane Pemphigoid

To determine the rate of positivity of immunofluorescence studies in buccal biopsies in patients with cicatrizing conjunctivitis undergoing workup for ocular mucous membrane pemphigoid (MMP)/ocular cicatricial pemphigoid (OCP). Retrospective cohort review. Forty-one patients with cicatrizing conjunctivitis undergoing workup for OCP. A retrospective chart review of direct immunofluorescence (DIF) studies in buccal mucosal biopsies was performed. The primary outcome measure was the rate of positivity of direct and indirect immunofluorescence studies on buccal mucosal biopsies. Twenty-two patients (54%) had a positive buccal mucosal biopsy; 64% of patients (14/22) demonstrated+DIF on initial biopsy and an additional 36% of patients (8/22) on the second biopsy. Eighteen patients underwent conjunctival biopsy. In the 6 patients with a negative conjunctival biopsy, 4 (67%) had a positive buccal biopsy. Buccal mucosal immunofluorescence studies may be positive in patients with OCP even in the absence of extraocular disease. Buccal mucosal biopsy may be considered as an alternative to or attempted before conjunctival biopsy for the diagnosis of OCP, particularly in patients in whom conjunctival biopsy may be difficult or imminently visually threatening.

Management Strategies of Juvenile Idiopathic Arthritis-Associated Chronic Anterior Uveitis: Current Perspectives.

Juvenile idiopathic arthritis (JIA) is the most common extraocular disease associated with pediatric uveitis. Despite the growing knowledge about the pathogenetic and clinical characteristics of the disease, it still remains a challenge for both the pediatric rheumatologist and ophthalmologist. Since uveitis is asymptomatic in most cases, it is generally detected by parents in a late phase of the disease when complications have occurred with consequent severe vision loss. Improvement in attentive screening and early treatment initiation to suppress inflammation has considerably reduced the sight-threatening outcomes of JIA-associated chronic anterior uveitis (JIA-CAU). Initial treatment with topical steroids is effective in most cases. However, more severe cases require the use of periocular or systemic corticosteroids, possibly leading to long-term complications. These include growth retardation, cataract and glaucoma. Systemic immunosuppressive agents are then employed in patients resistant to first-line therapy or to reduce steroid-associated complications. In this review, we will discuss the immunosuppressant agents currently employed for the treatment of the disease, including anti-tumor necrosis factor (TNF)α biologics approved or not by the regulatory agencies. We will also highlight how new therapeutic options like biologic targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) co-stimulatory molecule, interleukin-6 receptor (IL-6R) or B lymphocytes might represent exciting new options for patients resistant to conventional therapy. Finally, the potential use of janus kinase (JAK) inhibitors recently approved for the treatment of several inflammatory rheumatic diseases in adults will be also discussed.

Clinicoepidemiological Profile and Treatment Outcomes in Children with Retinoblastoma: Experience from a Cancer Care Center in Northeast India.

Gaurav KumarBackground Retinoblastoma (RB) is the most common primary intraocular malignancy in children. We sought to provide a comprehensive assessment of epidemiological profile and treatment outcomes of children with RB. Methods In this retrospective study, we analyzed 189 children diagnosed with RB at our center between 2004 and 2017. Survival was analyzed with the Kaplan-Meier method and log-rank test. Results Median age at presentation was 14 months with male: female ratio 1.2:1. Mean duration between onset of symptoms and presentation was 49 days (standard deviation ± 79). Most common presenting symptom was white pupillary reflex in 60% of children. Family history of RB and other cancers was found in one (0.5%) and seven (4%) children, respectively. Primary mode of diagnosis and staging was ocular ultrasonography (bone scan) in 87% of patients. Computed tomographic scan and magnetic resonance imaging were done in 124 (66%) and 30 (16%) patients, respectively. International staging system grade E disease was found in 144 (76%), extraocular disease in 55 (29%), bilateral disease in 49 (26%), and trilateral disease in 3 (1.5%) children. Out of 189 children with RB, 33 (18%) refused treatment and 156 children received treatment (24 children [15%] abandoned treatment midway and 132 [85%] completed treatment). One hundred children (64%) received systemic therapy as neoadjuvant or adjuvant chemotherapy and 20 (13%) received local therapy. Eyeball and vision salvage rate with chemotherapy were 20 (13%) and 9 (6%), respectively. Cryotherapy was the most common modality of local treatment used in 11 (55%) children. Five-year survival for patients who received treatment was 76% (median survival not reached). In the treatment refusal group, median survival was 9 months. Conclusion In developing countries, RB is mostly detected in advanced stages resulting in poor outcomes. Increased awareness and accessibility to dedicated centers for treating childhood malignancy can lead to early diagnosis, better prognosis, and increased vision salvage.

Retinoblastoma in Calabar Nigeria: An 18-Month Retrospective Review of Clinical Presentation at a Tertiary Eye Center

Background: Retinoblastoma, although rare, is the most frequently occurring primary intraocular tumor of childhood. While a cure is often achieved where appropriate treatment is instituted early in the disease, late presentation often leads to unsuccessful treatment interventions. Aim: The aim of this study is to provide baseline information on the clinical presentation of retinoblastoma as seen in a tertiary pediatric eye care facility in Calabar, Nigeria. Materials and Methods: A retrospective review of case files of children presenting to the Calabar Children's Eye Center (CCEC) with retinoblastoma over 18 months from January 1, 2018 to June 30, 2019 was done. Results: Data were collected from 39 children with retinoblastoma who met the inclusion criteria. There were 22 (56.4%) males and 17 (43.6%) females, and the age range was 7–41 months, with a mean age of 25.6 (±9.0) months. Unilateral disease was seen in 27 (69.2%) participants, whereas 12 (30.8%) had bilateral disease. Although multiple symptoms were seen in many participants protrusion of eye was the most frequently occurring first symptom, (17, 44.0%) followed by red eye (13, 33.0%), whitespot in eye (5, 13.0%), and abnormal alignment (4, 10.0%) among study participants. The lag time from recognition of symptoms to initial consultation ranged from 1 to 25 months, with a mean lag time of 9.13 ± 5.68 months. The ICRB classification system was most frequently used, 27 (69.2%), followed by cTNMH 11 (28.2%), and International Intraocular Retinoblastoma Classification 1 (2.6%). The International Retinoblastoma Staging System was representative. Of the 78 eyes studied, (51, 65.3%) had different stages of retinoblastoma with the majority presenting as advanced retinoblastoma (46, 90.2%). Conclusions: Retinoblastoma is seen at the CCEC. Although the most frequent symptom was protrusion of eye, the lag time was often several months long. Most patients presented late with advanced ocular retinoblastoma and or extraocular disease.