Orbital Development in Children with Retinoblastoma: An Imaging-Based Study.

PURPOSE: To examine whether children treated for Retinoblastoma (Rb) have impaired orbital development. METHODS: A retrospective case series was performed among children with Rb treated at a single medical center from 2004 to 2020. Orbital volumes and measurements were assessed by 3-dimensional image processing software. The main outcome measures were differences in orbital growth between Rb and non-Rb eyes assessed at last follow-up. RESULTS: Among 44 patients included (mean age 16.09 ± 18.01 months), a positive correlation between age and orbital volume was observed only in the uninvolved, healthy eyes (p = .03). In unilateral cases, orbital growth in the horizontal, vertical, and depth planes was smaller on the affected side compared to the healthy eyes (p < .05). Orbits that underwent enucleation showed decreased growth over time compared to those treated conservatively (p = .017). CONCLUSIONS: Orbital growth rate is slower in the orbits of children treated for Rb compared to healthy orbits. Enucleation negatively affects orbital growth.

Effects of photoperiod and food on glucose intolerance and subsequent ocular pathology in the fat sand rat.

Type 2 diabetes mellitus (T2DM) and its ocular complications, such as cataract and diabetic retinopathy (DR) have been linked to circadian rhythm-disturbances. Using a unique diurnal animal model, the sand rat (Psammomys obesus) we examined the effect of circadian disruption by short photoperiod acclimation on the development of T2DM and related ocular pathologies. We experimented with 48 male sand rats. Variables were day length (short photoperiod, SP, vs. neutral photoperiod NP) and diet (standard rodent diet vs. low-energy diet). Blood glucose, the presence of cataract and retinal pathology were monitored. Histological slides were examined for lens opacity, retinal cell count and thickness. Animals under SP and fed standard rodent diet (SPSR) for 20 weeks had higher baseline blood glucose levels and lower glucose tolerance compared with animals kept under NP regardless of diet, and under SP with low energy diet (SPLE). Animals under SPSR had less cells in the outer nuclear layer, a lower total number of cells in the retina, and a thickened retina. Higher blood glucose levels correlated with lower number of cells in all cellular layers of the retina and thicker retina. Animals under SPSR had higher occurrence of cataract, and a higher degree of cataract, which correlated with higher blood glucose levels. Sand rats kept under SPSR develop cataract and retinal abnormalities indicative of DR, whereas sand rats kept under NP regardless of diet, or under SPLE, do not. These ocular abnormalities significantly correlate with hyperglycemia.

Diffuse choroidal hemangioma in pregnancy: Symptomatic diffuse choroidal hemangioma spontaneously resolving postpartum.

We present the case of a pregnant young woman with symptomatic diffuse choroidal hemangioma (CH), diagnosed with Sturge-Weber syndrome (SWS). Three months postpartum, there was full spontaneous resolution of the subretinal fluid and improvement in the visual acuity (VA). A 29-year-old, 31-week pregnant female with a coagulation disorder and enoxaparin (clexane) treatment, complained of a left visual disturbance of 2 weeks duration. On examination, the right eye was normal; left eye VA was 6/12 (20/40) with a left eyelid port-wine stain and on funduscopic examination there was a serous retinal detachment. On ultrasound, there was diffuse thickening of the choroid with a focus superior and nasal to the disc with active vascularization - a diagnosis of diffuse CH was made. Magnetic resonance imaging (MRI) and MR venography studies of the brain and orbit revealed engorged orbital vasculature, and the diagnosis of SWS was made. Three months after Cesarean section with birth of a healthy baby boy, VA returned to 6/9 with full resorption of subretinal fluid. On fundoscopic exam, there were no retinal or vein occlutions but there were tortuous blood vessels with A-V crossing. This is a rare case of newly diagnosed SWS with symptomatic diffuse CH in pregnancy. Postpartum, there was full resolution of the subretinal fluid. A watchful waiting approach can be considered in such cases.

Autoimmune disorders caused by intravesical bacillus Calmette-Guerine treatment: A systematic review.

Intravesical bacillus Calmette-Guérin (BCG) is a common and highly effective treatment for non-muscle invasive urothelial carcinoma of the urinary bladder. BCG may cause an autoimmune reaction in some patients. One hundred and fifty-eight papers were analyzed, for a total of hundred and thirty patients with reactive arthritis, sixty patients with ocular manifestations and eighteen patients with other rheumatologic diseases. Among 130 subjects with reactive arthritis, an autoimmune symptom occurred after 5 instillations of intravesical BCG (IQR 4-6), which represents 5 weeks in most cases. Fifty-one patients had concurrent ocular involvement. The resolution of symptoms was achieved in a median of 32.5 days (IQR 14-90). Forty-two men and twenty women had ocular manifestations, most commonly conjunctivitis. Patients with HLA-B27 typing had earlier presentation of ocular symptoms related to the number of instillations (4.5 vs 6 [p < 0.05]. Resolution of symptoms was achieved at a median of 128 days (IQR 21-150). Among patients treated with NSAIDs (either with or without steroids), the duration of the disease was significantly shorter in both the articular and the ocular groups (28 vs. 120 [p < 0.05] and 30 vs.105 [p < 0.05], respectively). Other autoimmune manifestations included general autoimmune diseases, such as vasculitis, psoriasis and myasthenia gravis.

Ocular Behçet Disease-Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset.

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18-39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar.

Retinal vascular occlusions in ocular Behçet disease - a comparative analysis.

PURPOSE: The literature on retinal vascular occlusions in Behçet disease (BD) patients is limited. The aim of this study is to thoroughly investigate retinal vascular occlusions among ocular BD patients. METHODS: Retrospective, multicentre case-control study. Three-hundred and three eyes of 175 patients with ocular BD, from 13 hospitals in Israel and Palestine, were included. Patients were assigned into two groups according to the presence of retinal vascular occlusion. Epidemiology, systemic and ocular manifestations, treatments and outcomes were compared between the groups and risk factors for retinal vascular occlusions were identified. RESULTS: One hundred twenty-five patients (71.4%) were male. The mean age at presentation was 28.2 ± 0.86 years. Retinal vascular occlusions were found in 80 eyes of 54 (30.9%) patients, including branch retinal vein occlusion (51.3%), peripheral vessels occlusions (32.5%), central retinal vein occlusion (13.8%) and arterial occlusions (7.5%). Systemic manifestations were similar among both groups. Anterior uveitis was more common in non-occlusive eyes (p < 0.01). Non-occlusive retinal vasculitis (p = 0.03) and ocular complications were more common in occlusive eyes (p < 0.01). Treatments including mycophenolate mofetil, Infliximab or a combination therapy of anti-metabolite and calcineurin inhibitor were more commonly used by occlusive patients (p < 0.05). Occlusive patients underwent more cataract surgeries (p = 0.03). The occlusive group had worse mean best-corrected visual acuity (BCVA) throughout follow-up (p < 0.01). Risk factors for retinal vascular occlusions included male sex and Jewish ethnicity (p < 0.05). CONCLUSION: Retinal vascular occlusions were found in a third of ocular BD patients. Occlusive eyes had a worse prognosis. Risk factors for vascular occlusions were identified.

Herpetic Eye Disease Following the SARS-CoV-2 Vaccinations.

PURPOSE: To describe herpetic ocular infections following SARS-CoV-2 vaccinations. METHODS: A retrospective study of herpetic ocular infections after BNT162b2mRNA vaccination and a literature review. RESULTS: A cohort of five patients: three varicella zoster virus (VZV) and two herpes simplex virus (HSV) cases, as well as 19 literature cases: 9 cases of VZV and 10 cases of HSV post BNT162b2mRNA, AZD1222, mRNA-1273, and CoronaVac vaccinations. All cases presented within 28 days post vaccination. Most VZV and HSV cases (15/19) reported in the literature presented post first vaccine dose, while in our cohort 2 VZV cases presented post second dose and both HSV cases and one VZV case post third dose. The most common presentations were HZO with ocular involvement and HSV keratitis. All eyes had complete resolution; however, one had retinal detachment and three corneal scars. CONCLUSION: Herpetic ocular infections may develop shortly after SARS-CoV-2 vaccinations. Overall, the outcome is good.

Amelanotic conjunctival melanoma in a child.

Purpose: Malignant melanomas of the conjunctiva are extremely rare in children. In this case report we present a conjunctival melanoma of a child. Observations: We report a case of a 7 years old boy who presented with a rapidly growing reddish lesion measuring 8mm in base × 2.5 mm in thickness on the nasal conjunctiva in his right eye. The patient underwent resection of the lesion (with 4 mm margins of the surrounding clinically normal conjunctiva) and cryotherapy to the adjacent conjunctival margins. Histopathology confirmed the diagnosis of conjunctival melanoma. Pathology also can be challenging; a review of pathology is advisable as happened in this case. Systemic workup was negative for metastatic disease. On 73 months of follow up, the patient was stable without local recurrence or secondary systemic disease. Conclusions and Importance: Malignant melanoma can present de novo as an amelanotic rapidly growing conjunctival lesion in children. This case should raise the awareness of the variable clinical presentations, the challenging diagnosis, treatment and follow up of pediatric conjunctival melanoma.

Peripheral Exudative Hemorrhagic Chorioretinopathy with and without treatment-Clinical and multimodal imaging characteristics and prognosis.

PURPOSE: To describe clinical and imaging characteristics of patients with Peripheral Exudative Hemorrhagic Chorioretinopathy (PEHCR), prognosis and treatment response. METHODS: In this retrospective cohort study medical records of patients diagnosed with PEHCR in a tertiary medical center between 2008 and 2018 were reviewed. Collected data included demographics, medical history, ophthalmologic examination and multi-modal imaging including fundus autofluorescence, optical coherence tomography (OCT), ultrasound (US), fluorescein angiography and indocyanine green angiography when available. Bevacizumab treatment results were analyzed when applied. RESULTS: 35 eyes of 32 patients were included, with a female predominance (56.25%) and an average age of 79.0±9.87 years at presentation. Most common OCT and US findings were subretinal mass (68.75%), pigment epithelial detachment (30.00%) and atrophic changes (21.86%). Median follow-up period was 18.00 months (range 0-102). Visual acuity (VA) remained stable (39.29%) or improved (25.00%) in most cases available for follow-up. Treatment with intravitreal bevacizumab induced a statistically significant clinical resolution in 88.89% of eyes available for follow-up (8/9 eyes) (p = 0.02). CONCLUSIONS: PEHCR is presented with high clinical variability and generally good prognosis. This is the first publication demonstrating a statistically significant clinical resolution of disease following intravitreal bevacizumab injections.

Uveitis prior to clinical presentation of Multiple Sclerosis (MS) is associated with better MS prognosis.

OBJECTIVE: An association between uveitis and multiple sclerosis (MS) is well-established, but the actual nature of that association remains poorly understood. We sought to determine the association between the presence of a uveitis diagnosis prior to an MS diagnosis compared to no pre-existing uveitis diagnosis in MS patients. METHODS: Patients in whom the presentation of uveitis preceded the presentation of MS (study group) and patients with MS and no uveitis (control group) were randomly selected at a ratio of 1:3 from the Sheba Multiple Sclerosis Center computerized database. RESULTS: Eleven patients presented with uveitis prior to MS diagnosis (study group), and 31 randomly selected patients had MS without uveitis (control group). Only one patient in the study group deteriorated to EDSS 3 during the follow-up period, compared to 15 patients in the control group (9.1% vs 48.4%, P = 0.049). None of the patients in the study group reached EDSS 6 during the 10 years of follow-up compared to 6 (19.4%) patients in the control group (P = 0.194). CONCLUSIONS: MS patients who presented with uveitis that preceded their neurological symptoms of MS demonstrated a clinically significant better neurological prognosis, than our MS patients with no uveitis.

Mammalian target of rapamycin inhibitors for the treatment of astrocytic hamartoma in tuberous sclerosis complex (TSC).

PURPOSE: Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder. Fifty percent of patients with TSC will develop retinal astrocytic hamartoma (RAH). The mammalian target of rapamycin (mTOR) inhibitors interferes with the pathological mechanisms of TSC. Treatment of RAH with mTOR inhibitors has been described in only a few isolated case reports. The purpose of this study was to assess the effect of mTOR inhibitors on RAH in a small cohort of patients. METHODS: The medical records of all consecutive patients with ocular manifestations of TSC that were treated with mTOR inhibitors at the Sheba Medical Center from January 2014 to December 2018 were retrospectively reviewed. Data collection included demographics, medical history, ocular presentation, ocular treatment, and treatment outcome. Tumor size was assessed by a masked observer, before and after treatment. Lesion measurements were made with Heidelberg SD-OCT (HRA + OCT SPECTRALIS), and fundus photos were taken with RetCam3® (Natus, USA) and analyzed by "ImageJ" software. RESULTS: Eleven patients with tuberous sclerosis and astrocytic hamartoma were treated with mTOR inhibitors in the study period. Of them, 6 children (11 eyes, 20 tumors) had proper imaging of tumor size before and after treatment. The analysis included these 11 eyes. All six patients had non-ocular manifestations of TSC, including dermatologic (n = 5), neurologic (n = 5), and renal (n = 3) involvement. Ocular involvement included in five eyes (45%) tumors near the optic disc and in four eyes (37%) foveal tumors. The mean follow-up duration was 2.15 ± 1.4 years (range 10 months to 4.5 years). The average tumor base reduction in the treated group was 17.8% ± 15.9. The average maximal thickness at baseline was 414 ± 174 µm (range 152-686 µm). There was a 14% ± 7.1 reduction after treatment. None of the tumors showed evidence of growth at the final follow-up. CONCLUSION: The findings of this study suggest that mTOR inhibitors can reduce tumor size and that they can be considered as an optional treatment in certain conditions. This preliminary report is the first to quantitatively assess pre- and posttreatment tumor size, in young patients.

Beneficial effects of voluntary wheel running on activity rhythms, metabolic state, and affect in a diurnal model of circadian disruption.

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the "circadian syndrome" and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.

Publication trends in clinical ophthalmology journals in the last decade.

PURPOSE: To examine the absolute number and the proportions of articles published in general high-ranked ophthalmology journals for each ophthalmic subspecialty during the last decade, and to examine the publishing trends over the study period. METHODS: All original articles published between January 2010 and December 2019 in the selected general clinical ophthalmic journals were included in the study. All abstracts of original articles were reviewed and deemed to be related to 1 of the 11 ophthalmic subspecialties. RESULTS: Six journals and 10,232 abstracts were reviewed. Articles focused on medical retina were the most common in the last decade (35.22%) while articles focused on strabismus were the least common (2.11%). The total number of articles published per year decreased during the last decade (p < 0.01). There was a significant reduction in the number of publications per year focused on anterior-chamber (p = 0.012), cataract and refractive-surgeries (p = 0.014), oculoplastic (p < 0.01), and strabismus (p = 0.011). In each year during the last decade, the highest proportion of publications was focused on medical retina while the lowest proportion of publications in most of the years was focused on strabismus. There was a significant decrease during the years in the proportion of articles focused on oculoplastic (p < 0.01). CONCLUSIONS: During the last decade, there have been differences in the proportion of publications of different ophthalmology subspecialties in high impact factor journals. This probably derives from demographic changes and advances in diagnosis and treatment. The proportion of articles focused on medical retina was the highest during all years while the proportion of articles focused on strabismus was consistently the lowest.

Anterior chamber infiltration of CAR T-cells.

A unique image of anterior chamber infiltration in a 2-year-infant with leukemia, treated with CD19 CAR T cells. Despite significant lymphopenia and resemblance of fungal infection initially, biopsy and cytologic analysis from anterior chamber fluid confirmed that this was CAR T-cell infiltration, likely targeting microscopic leukemia, unknown to us treating physicians. This is a unique case in 2 aspects: first, to state the high quality of CAR T-cell trafficking; and second - given the wide use of these cells currently, this image may help educate clinicians regarding this potential diagnosis.

UVEITIS AFTER THE BNT162b2 mRNA VACCINATION AGAINST SARS-CoV-2 INFECTION: A Possible Association.

PURPOSE: To describe uveitis cases after the BNT162b2 mRNA SARS-CoV-2 vaccination. METHODS: This is a multicenter, retrospective study. Vaccine-related uveitis diagnosis was supported by the classification of the World Health Organization Adverse Drug Terminology and the Naranjo criteria. RESULTS: Twenty-one patients (23 eyes) with a mean age of 51.3 years (23-78 years) were included. Eight of the 21 patients had a known history of uveitis. The median time from previous to current attack was 1 year (0.5-15 years). There were 21 anterior uveitis cases, two with bilateral inflammation. Eight cases occurred after the first vaccination and 13 after the second vaccination. All but three presented as mild to moderate disease. Two patients developed multiple evanescent white dot syndrome after the second vaccination. The mean time from vaccination to uveitis onset was 7.5 ± 7.3 days (1-30 days). At final follow-up, complete resolution was achieved in all but two eyes, which showed significant improvement. One case of severe anterior uveitis developed vitritis and macular edema after the second vaccination, which completely resolved after an intravitreal dexamethasone injection. CONCLUSION: Uveitis may develop after the administration of the BNT162b2 mRNA vaccine. The most common complication was mild to moderate anterior uveitis, while multiple evanescent white dot syndrome can also occur less frequently.

Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG).

INTRODUCTION: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. METHOD: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. RESULTS: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. CONCLUSION: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.