Development of New Solitary Retinoblastoma Tumors during and after Chemotherapy

Purpose@#To review the occurrence of new solitary tumors during and after intravenous chemotherapy against retinoblastoma. @*Methods@#From 115 eyes of 78 patients with a diagnosis of intraocular retinoblastoma who underwent intravenous chemotherapy and focal treatment without prior treatment, patient demographics, age at diagnosis, laterality, classification (Reese-Ellsworth and International Classification of Retinoblastoma), and treatment options were recorded. In addition, the occurrence of small tumors during and after chemotherapy was documented with a detailed review of medical records and fundus photographs. @*Results@#Of a total of 115 eyes of 78 consecutive patients, new solitary tumors were observed in 50 eyes (50 / 115, 43%) of 40 patients (40 / 78, 51%). Multinominal logistic regression analyses showed that age at diagnosis (before 1 year) and vitreal seeding at diagnosis were linked to the development of isolated and miliary tumors, respectively. Kaplan-Meier analyses demonstrated that all small tumors developed with 20 months from the start of chemotherapy. Twenty-eight eyes (28 / 34, 82%) were salvaged with additional focal treatment in 34 eyes with isolated tumors. @*Conclusions@#Small tumors were observed during and after chemotherapy against retinoblastoma in patients who underwent intravenous chemotherapy and focal treatment. It is necessary to promptly identify and address small tumors for the preservation of eyeball and vision.

Toward the Clinical Application of Therapeutic Angiogenesis Against Pediatric Ischemic Retinopathy

Therapeutic angiogenesis refers to strategies of inducing angiogenesis to treat diseases involving ischemic conditions. Historically, most attempts and achievements have been related to coronary and peripheral artery diseases. In this review, we propose the clinical application of therapeutic angiogenesis for the treatment of pediatric ischemic retinopathy, including retinopathy of prematurity, familial exudative retinopathy, and NDP-related retinopathy. These diseases are all characterized by the reduction of physiological angiogenesis and the following induction of pathological angiogenesis. Therapeutic angiogenesis, which supplements insufficient physiological angiogenesis, may be a therapeutic approach for ischemic conditions. Various molecules and modalities can be utilized to apply therapeutic angiogenesis for the treatment of ischemic retinopathy, as in coronary and peripheral artery diseases. Experiences with cardiovascular diseases provide a useful reference for the further clinical application of therapeutic angiogenesis in pediatric ischemic retinopathy. Recombinant proteins and gene therapy are powerful tools to deliver angiogenic factors to retinal tissues directly. Furthermore, endothelial progenitor or bone marrow-derived cells can be injected into the vitreous cavity of the eye for therapeutic angiogenesis. Intraocular injections are highly promising for the delivery of therapeutics for therapeutic angiogenesis. We expect that therapeutic angiogenesis will be a breakthrough in the treatment of pediatric ischemic retinopathy.

Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

Clinical Characteristics of Retinoblastoma Patients whose Diagnosis was Difficult due to Atypical Ocular Manifestation

PURPOSE: To report the clinical characteristics of retinoblastoma patients whose diagnosis was difficult due to atypical ocular manifestations. METHODS: Among retinoblastoma patients who were diagnosed and treated from January 1999 to December 2014 at Seoul National University Children's Hospital, 6 patients whose diagnosis was difficult were retrospectively reviewed. Factors including age, sex, family history, initial findings, time to final diagnosis, histopathologic examination, additional treatment, and survival rate were evaluated. RESULTS: Among 6 patients, 5 were male, and the mean age at the initial visit was 32.9 ± 19.1 months. None of the patients had family history, and all presented with unilateral lesion at the initial visit. The initial diagnoses were Coats' disease and uveitis in 2 patients, respectively, and persistent hyperplastic primary vitreous and traumatic hyphema in 1 patient, respectively. During an intensive short-term follow-up of 8.3 ± 5.3 weeks, 2 patients showed malignant cells after external subretinal fluid drainage procedure, and 4 patients demonstrated increasing ocular size or calcification in imaging. These patients received enucleation under suspicion of malignancy and were finally diagnosed with retinoblastoma after histopathologic examination. There were 2 patients with optic nerve involvement, and 3 patients underwent additional systemic chemotherapy. Five patients were followed-up for 7.6 ± 6.3 years after enucleation, and the mean age at final follow-up was 10.6 ± 7.4 years. CONCLUSIONS: Retinoblastoma is one of the diseases in which early diagnosis and treatment are important. However, some cases are difficult to diagnose, even for experienced clinicians. If there are no typical manifestations such as mass or calcification and early findings show retinal detachment, glaucoma, pseudohypopyon, or hyphema, intensive short-term follow-up to exclude retinoblastoma is needed.

Superficial Punctate Keratoepitheliopathy Under Treatment with Erlotinib and Lapatinib

PURPOSE: To report the corneal superficial punctate keratoepitheliopathy in 2 patients taking the epidermal growth factor receptor (EGFR) inhibitors, erlotinib and lapatinib, respectively. CASE SUMMARY: Case 1, who received erlotinib, showed trichomegaly without touching the cornea and diffuse punctate keratoepitheliopathy. Corneal epitheliopathy and the corresponding symptoms resolved after discontinuation of the drug then recurred with reapplication. Case 2 presented diffuse corneal punctate epithelial erosions that developed without any cilia involvement after the patient was administered lapatinib. The visual acuity of both patients was not severely diminished and keratoepitheliopathy was mostly resolved with the treatment of preservative-free artificial tears and autologous serum eye drops. CONCLUSIONS: Erlotinib and lapatinib are both likely to cause visually tolerable corneal punctate keratoepitheliopathy which can be resolved with appropriate topical treatment.

The Clinical Characteristics of Optic Neuritis in Korean Children

PURPOSE: To study the clinical characteristics of optic neuritis in Korean children. METHODS: A retrospective review of the medical charts of 20 patients who were diagnosed with optic neuritis before age 10 was conducted in this study. Data were collected on the demographics, clinical features, use of intravenous corticosteroids, neuroimaging, and diagnosis of multiple sclerosis. RESULTS: The mean age at diagnosis was 6.5 +/- 1.8 years (range, 3 to 9 years). Seventeen patients (85%) were female, and 13 patients (65%) exhibited bilateral diseases. Visual acuity had decreased to or =20 / 40 in 16 of the 20 patients. The mean duration between the worst visual acuity and 20 / 40 was 2.30 +/- 2.91 months. Intravenous corticosteroid treatment was performed in 15 patients and exerted a beneficial effect on the visual outcomes. Disc swelling was observed in 75.8% of the affected eyes. Multiple sclerosis was diagnosed in five patients with a mean follow-up period of 21.9 +/- 20.3 months. The presence of lesions in brain magnetic resonance images was identified as the most significant factor with regards to the occurrence of multiple sclerosis. CONCLUSIONS: In children with optic neuritis, a profound decrease in initial visual acuity and rapid recovery of visual acuity were confirmed. Corticosteroid treatment resulted in a beneficial effect on visual outcomes, but had no effect on the risk of multiple sclerosis.

Effects of Botulinum Toxin A Injection into Salivary Glands of Patients with Brain Lesion Suffering from Posterior Drooling

OBJECTIVE: The aim of the study was to evaluate the effectiveness of ultrasouond-guided salivary gland injection of botulinum toxin A (BTX-A) for posterior drooling. METHOD: 11 patients with brain lesion (9 cerebral palsy, 1 hypoxic ischemic encephalopathy and 1 mental retardation) with posterior drooling (an initial PDAS score greater than 2) and related pulmonary problems were recruited. Drooling severity was measured at baseline, 4 weeks, 3 months and 6 months after botulinum toxin A injection, by using Teacher Drooling Scale (TDS), Visual Analogue Scales (VAS), Drooling Score System (DSS)-severity, frequency and Posterior Drooling/Aspiration System (PDAS). RESULTS: The TDS, DSS-severity, DSS-frequency, VAS, PDAS were significantly reduced at 4 weeks and 3 months after BTX-A injection into salivary glands compared to pre-injection (p<0.05). However, there were no significant changes at 6 months compared to pre-injection level. CONCLUSION: BTX-A injection into salivary glands may improve anterior drooling in patients with brain lesions. Furthermore BTX-A injection into salivary glands may also decrease the posterior drooling which might related to respiratory symptoms in aspiration pneumonia.

Analysis of Clinical Characteristics in Phlyctenular Keratoconjunctivitis at a Tertiary Center

PURPOSE: To report the clinical characteristics of patients with phlyctenular keratoconjunctivitis at a tertiary care center in Korea. METHODS: The authors of the present study retrospectively reviewed the medical records of 26 patients who were diagnosed with phlyctenular keratoconjunctivitis, identifying the age and sex at diagnosis, diagnosis of the referring clinic, laterality and location of the lesions, the results of bacterial cultures from the meibum, and treatment options. RESULTS: Eighteen patients (76.2%) were female, and the mean age at diagnosis was 18.4 +/- 10.5 years. Nine patients (34.6%) showed evidence of bilateral diseases, and corneal lesions were observed in 27 eyes of 21 patients. Bacterial cultures from the meibum were performed for 17 patients, with the following results: 6 cases of Staphylococcus epidermidis, 4 cases of Corynebacterium species, and 1 case of Propionibacterium acne. Neovascularization with corneal phlyctenules occurred from the inferior quadrant mostly. Twenty-four patients received the remission treatment of prednisolone acetate 1% eye drops and evidence of regression of new vessels was observed in all patients. Three patients (16.7%) experienced recurrence despite the maintenance treatment of cyclosporine 0.05% eye drops. Visual acuities improved significantly after the remission treatment, as compared to the initial visit. CONCLUSIONS: The phlyctenular keratoconjunctivitis patients who visited the tertiary center in Korea showed similar findings regarding demographics, involvement of blepharitis, and identified microorganisms, as compared with patients in previous reports. However, corneal lesions involving the visual axis were frequent, suggesting that with proper diagnosis and treatment, improvement in visual acuities is possible.

Leg Length Discrepancy Induced by Arterio-Venous Fistula Due to Repetitive Vascular Punctures: A case report

The causes of leg length discrepancy in childhood include neurologic, musculoskeletal, tumor and vascular diseases. It may contribute secondary complications such as gait disturbance, scoliosis, hip joint arthritis or cosmetic problem etc. Acquired arteriovenous fistula is a rare cause of leg length discrepancy. Multiple vascular punctures in the neonates, especially in prematures, can result in iatrogenic arteriovenous fistula formation. We report two cases of arteriovenous fistula secondary to vascular punctures, diagnosed by color doppler ultrasonography and CT angiography. The lesions were explored and treated surgically.

Surgical Treatment of Extensive Conjunctival Melanocytic Nevus Mimicking Conjunctival Melanoma

PURPOSE: To report a case of diffuse conjunctival melanocytic lesion mimicking conjunctival melanoma and treated by surgical excision and amniotic membrane transplantation. CASE SUMMARY: A 29-year-old man presented with diffuse pigmented lesion on the bulbar conjunctiva in the right eye, which had been present since birth. Circumferential pigmentation was observed in the perilimbal conjunctiva from 4 to 11 o'clock, and slightly elevated, dark brown-colored lesions with multiple small cysts were noted on the superior, inferior, and temporal bulbar conjunctiva. Incisional biopsy was performed from multiple sites to rule out conjunctival melanoma. Histopathologic examination showed small nevus cells and multiple cysts. Under local anesthesia, temporal conjunctival excision and amniotic membrane transplantation were performed. The surgical pathologist confirmed compound nevus. Four weeks after the surgery, full epithelialization was observed over the amniotic membrane. Several lesions were intentionally left during the surgery, and unnoticeable from the frontal view. The patient was satisfied with the surgical result. CONCLUSIONS: In extensive conjunctival pigmented lesion, biopsy should always be performed to rule out melanoma. Temporal conjunctival excision rather than whole lesion excision can be a cosmetically good surgical option for a diffuse conjuntival lesion proven as a benign conjunctival nevus.

Aspergillus fumigatus Scleritis Associated with Monoclonal Gammopathy of Undetermined Significance

A 68-year-old woman presented with pain in her left eye. Necrosis with calcium plaques was observed on the medial part of the sclera. Aspergillus fumigatus was isolated from the culture of the necrotic area. On systemic work-up including serum and urine electrophoresis studies, the serum monoclonal protein of immunoglobulin G was detected. The patient was diagnosed with monoclonal gammopathy of undetermined significance and fungal scleritis. Despite intensive treatment with topical and oral antifungal agents, scleral inflammation and ulceration progressed, and scleral perforation and endophthalmitis developed. Debridement, antifungal irrigation, and tectonic scleral grafting were performed. The patient underwent a combined pars plana vitrectomy with an intravitreal injection of an antifungal agent. However, scleral and intraocular inflammation progressed, and the eye was enucleated. Aspergillus fumigatus was isolated from the cultures of the eviscerated materials. Giemsa staining of the excised sclera showed numerous fungal hyphae.

Corneal Power Estimation Using Orbscan II Videokeratography in Eyes With Previous Corneal Refractive Surgeries

PURPOSE: To report three cases of corneal power estimation for intraocular lens power calculation using Orbscan II videokeratography in eyes with previous corneal refractive surgeries. CASE SUMMARY: In three eyes of three patients with previous corneal refractive surgeries, corneal power values were respectively measured at three, four, five, six mm-diameter zones of total mean, axial, tangential, and optical maps using Orbscan II videokeratography. Then, intraocular lens power values were calculated via the SRK/T formula. After cataract surgeries, back-calculated corneal power (BCK) values were estimated from post-phacoemulsification refraction data, and compared with those measured at three, four, five, six mm-diameter zones of each map in Orbscan II videokeratography. The postoperative refractive values after cataract surgeries were achieved within 1.5D of the target refraction in all eyes by using five mm total axial power and four mm total optical power for intraocular lens power calculation. Orbscan II parameters including three mm, four mm total axial power, and three mm total optical power were the least different from the BCK (0.69+/-0.49D, 1.08+/-0.54D, and 1.10+/-0.44D, respectively). CONCLUSIONS: If historical data are not available, Orbscan II videokeratography can be useful for estimating corneal power for intraocular lens power calculations in patients with previous corneal refractive surgeries.