Longitudinal follow-up of pediatric Graves' disease in preschool children: Clinical characteristics and a case report.

RATIONALE: Pediatric Graves' disease at preschool age is a rare condition. Previous reports have indicated that adolescents with this disease are girls. Pediatric Graves' ophthalmopathy in young children is rare, and long-term follow-up reports are lacking. PATIENT CONCERNS: The patient had hyperthyroidism and bilateral proptosis for 2 years, but she was only 4 years old. DIAGNOSES: The blood test revealed hyperthyroidism and the ophthalmic examination revealed proptosis. The patient had Graves' disease and Graves' ophthalmopathy. INTERVENTIONS: Initially, she was followed up in the pediatric department. Bilateral proptosis developed, and she was brought to the ophthalmology department for assistance. Orbital computed tomography revealed borderline enlargement of the extraocular muscles bilaterally. Other initial clinical findings included bilateral upper and lower eyelid trichiasis and mild punctate epithelial erosions of the cornea. She received conservative medical treatment in the ophthalmology department. OUTCOMES: Remission of hyperthyroidism was achieved 2 years after medical control. No elevated intraocular pressure, strabismus, or optic neuropathy developed during follow-up. Significant cosmetic improvement and gradual resolution of punctate epithelial erosions were found over 10 years. Finally, the patient had only mild bilateral lower trichiasis. LESSONS: Longitudinal follow-up revealed that the ocular manifestations of proptosis and eyelid trichiasis may have good outcomes. Proptosis gradually improved as the patient grew up.

Retinoblastoma in Taiwan: survival and clinical characteristics.

PURPOSE: To figure out the impact of national health insurance program and treatment modalities on the clinical outcomes of patients with retinoblastoma. STUDY DESIGN: Retrospective cohort study. METHODS: Enrolled patients were classified into three groups according to the time period in which their initial diagnosis was performed: patients diagnosed before 1995 (group 1), patients diagnosed in the time period 1995-2010 (group 2), patients diagnosed after 2010 (group 3). Comparison was made of clinical features including presenting signs, tumor spreading, and treatment modes. Survival and globe salvage rates were analyzed within each group. RESULTS: There were 157 patients (202 eyes) enrolled from 1978 to 2015. The overall mortality rate was 24.2%. The overall 5-year survival rate was 63.4%, 73.8%, 89.1% in the three time periods respectively (P = 0.007). The 5-year survival improved continuously in both unilateral and bilateral disease (P = 0.057; P = 0.015). Patients without extraocular spreading or diagnosed before 2 years of age had a better 5- year survival of 97.4% and 81.1% respectively. The globe salvage rate improved from 8.2%, 14.5%, to 35.1% (P < 0.001). The globe salvage rate was 46.9% in patients who received ophthalmic artery chemosurgery (OAC) and 6.4% in patients not received OAC. CONCLUSIONS: Improvement of survival and globe salvage rate was observed over time periods. National health insurance program has made medical care easily accessible to the public, leading to earlier diagnosis and treatment. Different treatment modes could achieve a better clinical outcome; among the new treatment modalities, OAC played an important role.

Clinical spectrum and treatment outcome of retinoblastoma with Group D and E diseases: A single institution retrospective review.

The purpose of our study was to evaluate the ocular survival and event-free survival after multimodal therapy for group D and E of retinoblastoma (RB). Enucleation of group D and E is controversial as the risks of chemotherapy must be weighed against the potential for vision.A 10-year retrospective study from one center of 86 patients with advanced intraocular disease defined as International Classification Retinoblastoma (ICRB) group "D" or "E." Cases with visible extraocular extension at diagnosis were excluded. Ocular survival and patient survival were assessed. Indirect ophthalmoscopy at examination under anesthesia to visualize the tumor was used to evaluate clinical response.The median onset age in 86 patients with group D or E eye was 16 months (1-167 months). There were 29 (34%) bilateral cases. Leukocoria was the most common presentation sign (61%). Chemoreduction was primarily used in the treatment of intraocular RB. Selective ophthalmic arterial injection (SOAI) was applied as a component of multimodal therapy in 34 of the 86 cases. The globe preservation rate in patients with group D or E eyes was 19%. Using chemoreduction for advanced eyes, more eyes are being preserved which enables 70% 5-year ocular survival in patients with group D eyes.In triaging appropriate patients, multidisciplinary strategy can reduce tumor size with chemoreduction and consolidate the regressed tumor with local ophthalmic therapy to ensure globe salvage.

Histopathologic findings after selective ophthalmic arterial injection of melphalan for retinoblastoma.

PURPOSE: The aim is to describe histopathologic observations in eyes enucleated after selective ophthalmic arterial injection (SOAI) of melphalan for retinoblastoma (RB). STUDY DESIGN: This is retrospective clinical study. PATIENTS AND METHODS: Histopathologic analysis of 14 eyes (13 patients) from May 2008 through January 2015 at Chang Gung Memorial Hospital. RESULTS: The eyes after SOAI were enucleated due to tumor viability (n = 7, 2 with vitreous hemorrhage), neovascular glaucoma (n = 4), lens drop to vitreous with total hyphema and elevated intraocular pressure (n = 1), retinal detachment (RD) progressed (n = 1), and persistent RD with phthisis change (n = 1). Almost all of the eyes showed vitreous seeding (n = 11 eyes) before treatment. After the treatment of SOAI, the histopathological examination revealed complete regression in four eyes with one was clinically diagnosed as viable tumor and progression, one with RD progression, and two as neovascular glaucoma. Six eyes showed invasion into the optic nerves, reaching the lamina cribrosa in five eyes, and six eyes with invasion into the choroid were observed. All of the cases with lamina cribrosa involvement showed tumor progression before enucleation, four cases with lamina cribrosa involvement expired later. CONCLUSION: Although some cases of RB can be controlled effectively with SOAI, but for refractory cases after SOAI, earlier decision of enucleation may be needed.

Macular Thickness, Foveal Volume, and Choroidal Thickness in Amblyopic Eyes and Their Relationships to the Treatment Outcome.

PURPOSE: To assess the correlations between the retinal/choroidal structure and the treatment outcomes of amblyopic children. METHODS: This study enrolled eyes with amblyopia resulting from strabismus, anisometropia, or ametropia. All patients underwent detailed eye examinations, including spectral domain optical coherence tomography (SD-OCT) scan. All of the subjects received amblyopic treatment and were divided into 2 groups after 6 months of follow-up: the recovered amblyopic group with a best-corrected visual acuity (BCVA) ≥0.8 and the persistent amblyopic group with a BCVA <0.8 on the Landolt C chart. RESULTS: Forty-four amblyopic children were included, of which 26 were in the recovered amblyopic group after 6 months of follow-up. The patients with strabismic anisometropic amblyopia and severe amblyopia (initial VA ≤ 0.3) were significantly predisposed to developing persistent amblyopia (P=0.049 and P < 0.001, respectively). After correcting with Littmann's formula, the thickness and volume of the parafoveal and perifoveal retinal regions in the persistent amblyopia group did not show significant differences with the recovered amblyopia group. CONCLUSIONS: The initial severity of amblyopia and the type of amblyopia were the risk factors related to the poor outcome of amblyopic treatment. The foveal thickness, foveal volume, and choroidal thickness were not associated with the treatment outcome.

Oculomotor palsy as a single presenting sign of midbrain hemorrhage.

We report a case presenting with bilateral oculomotor nerve palsy (ONP) resulting from a midbrain hemorrhage. The patient visited the ophthalmological clinic due to the sudden onset of horizontal diplopia for a week. Bilateral ONP spared the left eye levator and bilateral pupils were found while the remaining results of examinations were unremarkable. Cerebral magnetic resonance imaging revealed a midbrain hemorrhage. Mono-ocular occlusion was arranged, and the patient was referred to a neurologist for further management. No further ophthalmic signs developed, but the patient became bedridden due to brainstem hemorrhage and died of aspiration pneumonia 9 months after the onset of the oculomotor signs. It is advocated that midbrain hemorrhage should be included in the differential diagnosis once diplopia develops and that careful neurological investigation of the origin of diplopia is warranted.

Factors affecting surgical outcome of intermittent exotropia.

PURPOSE: The purpose of this study was to investigate the factors affecting surgical outcome in intermittent exotropia. DESIGNS: This was a retrospective interventional study. METHODS: Intermittent exotropic patients who had undergone surgical correction with a postoperative follow-up period of 1 month or more were included in the study. Surgical success was defined as an alignment between 10 prism diopters (PD) of exotropia or 5 PD of esotropia at 1 month. After data collection, data were analyzed in SPSS version 23 software. The main outcome measures were the factors affecting surgical outcome. RESULTS: We included 101 patients, including 52 (51.5%) male and 49 (48.5%) female. Among them, 62 (61.4%) patients achieved surgical success. Undercorrection was the primary reason of surgical failure. Multivariate regression analysis showed that a larger preoperative angle of deviation was associated with unfavorable surgical outcome (P = 0.053, odds ratio [OR] =0.97, 95% confidence interval [CI] = 0.94-1.00), and the presence of postoperative day 1 (POD 1) diplopia correlated significantly with higher surgical success (P = 0.001, OR = 4.54, 95% CI = 1.80-11.43). The presence of POD 1 diplopia was highly associated with POD 1 esotropia (P = 0.005, OR = 7.26, 95% CI = 1.84-28.58). CONCLUSION: In intermittent exotropia, larger preoperative angle of deviation may predict a lower surgical success rate. Despite a worrisome issue, the presence of diplopia on first POD is associated with immediate postoperative alignment of esotropia and predicts a higher surgical success.

Management of diplopia with visual-field defects.

PURPOSE: The management of diplopia can be challenging in patients with a concurrent visual-field (VF) defect. We conducted a retrospective chart review to analyze and compare treatment outcomes for different types of VF defects. METHODS: A retrospective chart review. RESULTS: Seven patients with diplopia and VF defects were identified during the study. Four had bitemporal hemianopia, one had homonymous hemianopia, and two had a constricted central VF. A favorable or satisfactory outcome was achieved in all but two patients with bitemporal hemianopia. CONCLUSIONS: The hemifield-slide diplopia may develop in patients with bitemporal hemianopia or heteronymous altitudinal visual defects. Sensory abnormalities usually persist, even after elimination of ocular misalignment.

Comparison of the Retinal Microvascular Density Between Open Angle Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

Purpose: To compare optical coherence tomography angiography (OCT-A) retinal vasculature measurements between nonarteritic anterior ischemic optic neuropathy (NAION) and open angle glaucoma (OAG) with altitudinal hemifield visual field defects. Methods: This retrospective cross-sectional study included 10 NAION eyes and 16 OAG eyes, both demonstrating hemifield visual field defects, and 27 normal eyes serving as controls. The peripapillary and macular OCT-A scans were acquired. The retinal vessel density data were compared among NAION, glaucomatous, as well as control eyes. Results: There was statistically significant difference in peripapillary whole image vessel density (wiVD), circumpapillary vessel density (cpVD), macular wiVD, and perifoveal vessel density (pfVD) between the three groups (P < 0.05 for all). In comparison between OAG and NAION groups, the NAION group demonstrated marked decrease in average cpVD (P = 0.008) and in most sectors of cpVD except the inferior one, while the OAG group demonstrated significant decreased macular wiVD and pfVD (P = 0.03 and 0.003, respectively). Multivariate analysis indicated that average thickness of retinal nerve fiber layer was the only predictor for peripapillary wiVD and cpVD (P = 0.005 for both). By contrast, thickness of ganglion cell complex was the only predictor for macular wiVD (P = 0.007). Conclusions: OCT-A detected significant difference in peripapillary and macular retinal vessel densities between OAG and NAION eyes. These differences might provide comparative insight into the pathophysiology of these two diseases.

Retinal Vessel Density in Optical Coherence Tomography Angiography in Optic Atrophy after Nonarteritic Anterior Ischemic Optic Neuropathy.

Aims. To compare optical coherence tomography angiography (OCT-A) retinal vasculature measurements between normal and optic atrophy after nonarteritic anterior ischemic optic neuropathy (NAION) subjects. Design. This prospective observational study was conducted between July 2015 and August 2016 at the ophthalmology outpatient department of a referral center in Taiwan. Peripapillary (4.5 × 4.5 mm) and parafoveal (6 × 6 mm) OCT-A scans were acquired. Measurements of the peripapillary region were obtained in two areas: (1) circumpapillary vessel density (cpVD) and (2) whole enface image vessel density (wiVD). Results. 13 participants with optic atrophy after NAION had lower peripapillary vessel density than the 18 age-matched participants in the healthy control (HC) group (p < 0.001 for both cpVD and wiVD). However, the parafoveal vessel density was not significantly different between the two groups (p = 0.49). The areas under the receiver operating characteristic curve for the HC and NAION eyes were 0.992 for cpVD and 0.970 for wiVD. cpVD and wiVD were significantly correlated with the average retinal nerve fiber layer thickness (p < 0.001 for both). Conclusion. Peripapillary retinal perfusion is significantly decreased in optic atrophy after NAION. OCT-A may aid in the understanding of structure-function-perfusion relationships in NAION.

Cortical damage in the posterior visual pathway in patients with sialidosis type 1.

In order to identify the cortical changes in patients with Sialidosis type 1, diffusion tensor imaging and resting state fMRI were acquired from 11 patients and 11 sex/age matched normal controls after clinical evaluations. The neuroimages from each participant were normalized and parcellated according to the Automatic Anatomical Labeling. Both the mean diffusivity and the corresponding functional connectivity were calculated from each cortical region. The white matter tract integrity was examined. The difference between patients and controls was examined using Student's t-test and between patients with either homozygous or heterozygous mutations by Mann-Whitney U test, both at a threshold of 0.05. Increased mean diffusivity throughout the brain can be noticed in the patients, together with a compromised white matter tracts integrity. The most severely affected cortical regions are in the occipital lobe. Decreased functional connectivity was from the temporal and occipital lobes to the hippocampus and parahippocampus. In contrast, connectivity from thalamus was enhanced. Diffused cortical atrophy with posterior focal lesions was noticed. We concluded that MRI observed functional changes in the posterior cortical pathways in the patients with Sialidosis. The observation might be related to the cortical blindness due to an altered neural network and a compromised visual pathway in the patients.

Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report.

BACKGROUND: Controlling retinoblastoma with seeding is challenging despite advances in treatment modalities. Intravitreal melphalan is an alternative to external beam radiation or enucleation for recurrent or refractory vitreous seeds. Significant ocular side effects following intravitreal melphalan injections are uncommon. Complications have been reported in eyes receiving higher concentrations of melphalan and repetitive injections. We report a case in which diffuse chorioretinal atrophy was developed at the injection site after a single, standard low-dose intravitreal melphalan injection. CASE PRESENTATION: A 12-month-old female child without a family history of retinoblastoma presented with unilateral group C retinoblastoma in her right eye. A solitary tumour with retinal breaks on the tumour surface, and vitreous seeds overlying the tumour were observed at the 8 o'clock position of the retina. After two cycles of intra-arterial chemotherapy with melphalan, the main tumour displayed significant regression, but the vitreous seeds overlying the main tumour were still active. Because of the persistence of vitreous seeds and the inadequate response to intra-arterial melphalan treatment, intravitreal melphalan (8 µg in 0.05 mL) was injected using a 32-gauge needle 2.5 mm from the 5 o'clock position of the limbus, the meridian opposite to the vitreous seeds. After 1 month, the retina around the injection site demonstrated diffuse retinal pigment epithelium alterations with dense hard exudates. Although the main retinal mass, and vitreous seeds resolved, the hard exudates persisted for more than 2 years after the single low-dose melphalan injection. CONCLUSIONS: Intravitreal melphalan injections should be cautiously used for eyes with refractory seeds, particularly when multiple injections are required to control retinoblastoma seeds. Dose- related retinal toxicity could occur in pre-treated eyes even when a relatively low standard dose is used. Such patients should be followed up closely to monitor the treatment response and to assess potential delayed toxicity.

Retinoblastoma in Mongolia: Clinical characteristics and survival from 1987 to 2014.

BACKGROUND/PURPOSE: This study aims to describe the clinical characteristics and treatment outcome of retinoblastoma in Mongolian children. METHODS: Data of all children diagnosed with retinoblastoma at the National Center for Maternal and Child Health of Mongolia from 1987 to January 2014 were reviewed retrospectively. The ICRB classification was used. Survival characteristics of the cohort were analyzed. RESULTS: Retinoblastoma was diagnosed in 79 eyes of 64 cases during the study period. Median age of diagnosis was 24.5 ± 15.8 months. There were no differences in sex ratio, and 15 cases (23%) were bilateral. Forty-three (67%) patients were from rural areas. The more frequent clinical presentations were leukocoria in 50 (78%) patients, strabismus in 24 (38%) patients, and glaucoma in 21 (33%) patients. Sixty-one (95%) patients were diagnosed with Classification D or worse when presented to us. Due to late diagnosis in the majority of cases, unilateral and bilateral enucleations were performed in 48 (61%) eyes and 24 (30%) eyes, respectively; exenteration was done in three (4%) eyes. Fifty-two (81%) patients received chemotherapy and 13 (8.3%) patients underwent external beam radiation after enucleation. At the time of last follow-up, 52 (81%) patients were alive, five (8%) patients were dead, and seven (11%) patients had lost to follow-up or unknown vital status. The mean follow-up period was 121.5 months (range, 12-360 months). In five cases with immunohistochemistry analysis in the eye specimen, neuron-specific enolase-, Ki-67 protein-, and B-cell lymphoma 2-positive cells were found in all five (100%) cases and Rb protein was detected in three (60%) cases. CONCLUSION: Retinoblastoma in Mongolia is frequently diagnosed at late stages and has a poor outcome. These data show the importance of early pediatric eye examinations and better treatment of retino-blastoma in children younger than 3 years in Mongolia.

Clinical presentations of X-linked retinoschisis in Taiwanese patients confirmed with genetic sequencing.

PURPOSE: To investigate the clinical characteristics of X-linked retinoschisis (XLRS) and identify genetic mutations in Taiwanese patients with XLRS. METHODS: This study included 23 affected males from 16 families with XLRS. Fundus photography, spectral domain optical coherent tomography (SD-OCT), fundus autofluorescence (FAF), and full-field electroretinograms (ERGs) were performed. The coding regions of the RS1 gene that encodes retinoschisin were sequenced. RESULTS: The median age at diagnosis was 18 years (range 4-58 years). The best-corrected visual acuity ranged from no light perception to 20/25. The typical spoke-wheel pattern in the macula was present in 61% of the patients (14/23) while peripheral retinoschisis was present in 43% of the patients (10/23). Four eyes presented with vitreous hemorrhage, and two eyes presented with leukocoria that mimics Coats' disease. Macular schisis was identified with SD-OCT in 82% of the eyes (31/38) while foveal atrophy was present in 18% of the eyes (7/38). Concentric area of high intensity was the most common FAF abnormality observed. Seven out of 12 patients (58%) showed electronegative ERG findings. Sequencing of the RS1 gene identified nine mutations, six of which were novel. The mutations are all located in exons 4-6, including six missense mutations, two nonsense mutations, and one deletion-caused frameshift mutation. CONCLUSIONS: XLRS is a clinically heterogeneous disease with profound phenotypic inter- and intrafamiliar variability. Genetic sequencing is valuable as it allows a definite diagnosis of XLRS to be made without the classical clinical features and ERG findings. This study showed the variety of clinical features of XLRS and reported novel mutations.

Selective ophthalmic arterial injection of melphalan for intraocular retinoblastoma: a 4-year review.

PURPOSE: To describe tumor response and complications after selective ophthalmic arterial injection (SOAI) of melphalan for treatment of intraocular retinoblastoma. METHODS: A retrospective review of 17 eyes (12 patients) treated with SOAI of melphalan from January 2010 through December 2013 at Chang Gung Memorial Hospital. RESULTS: SOAI was successfully performed in 49 of 54 attempts. Six eyes underwent SOAI as the primary treatment and 11 eyes had previously been treated with other treatment modalities. Subsequent to SOAI, tumor regression was observed in 12 of 17 eyes, and vitreous seeding with complete or partial regression in ten of 15 eyes. Globe salvage was achieved in ten of 17 eyes, with three of four in group B and group C eyes, and seven of 13 in group D and group E eyes. Pancytopenia accompanied by neutropenic fever was observed in one case. Twelve eyes had local side effects, including lid edema (two eyes), third cranial nerve palsy (two eyes), sixth cranial nerve palsy (one eye), chorioretinal atrophy (six eyes), retinal arterial occlusion (three eyes), retinal detachment (one eye), and vitreous hemorrhage (seven eyes). Three cases with high-risk features, according to the histopathologic examination, had metastatic disease, and two of them died. CONCLUSIONS: SOAI of melphalan is an effective treatment for intraocular retinoblastoma, achieving high globe salvage in cases of advanced disease, but can be associated with significant ocular complications. Repetitive SOAI with delayed enucleation could increase the risk of metastasis when used in high-risk cases. Therefore, clinicians should consider the benefits and potential risks and use this new technique with caution.

Multimodal retinal imaging in achromatopsia.

PURPOSE: To investigate comprehensive image findings in a patient with incomplete achromatopsia. METHODS: Observational case report. RESULTS: A 12-year-old girl was referred to our clinic with nystagmus, photophobia, poor best-corrected visual acuity, and impaired color vision since she was 5 years old. Her best-corrected visual acuity was 20/200 for both eyes. The fundus photography showed macula mottling, and fundus autofluorescence imaging showed a bull's eye-like maculopathy. The spectral domain optical coherence tomography revealed decreased outer nuclear layer thickness and inner and outer segment loss beneath the subfoveal area. The electroretinogram showed extinguished cone responses with relatively well-preserved rod responses. CONCLUSION: Fundus autofluorescence and spectral domain optical coherence tomography may serve as screening tools for achromatopsia candidates, but the electroretinogram study remains the most reliable test for diagnosis.

Down-regulation of matrix metalloproteinase-9 by pyrrolidine dithiocarbamate prevented retinal ganglion cell death after transection of optic nerve in rats.

PURPOSE: To investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) inhibitor, on the expression of matrix metalloproteinases (MMP) and MMP-mediated apoptosis in retinal ganglion cells (RGCs) following the transection of the optic nerve (ON) in rats. MATERIALS AND METHODS: The ON of adult male Sprague-Dawley rats was transected. The expression of MMP-2, MMP-9, and NF-κB was measured by Western blot analysis and immunohistochemical analysis following transection. In situ zymography was also performed to localize gelatinolytic activity in the retinas. PDTC was injected intravitreally immediately following transection of the ON to evaluate the effect on the expression of NF-κB and MMP as well as its anti-apoptotic effect and neuroprotective effect on RGCs. RESULTS: Significant up-regulation of MMP-9, and NF-κB was observed 7 days post-transection; however, this was not observed for MMP-2. PDTC at concentrations of 0.5 mM suppressed the up-regulation of MMP-9 and NF-κB, inhibiting gelatinolytic activity in the RGC layer. Meanwhile, far fewer apoptotic RGCs were detected and more surviving RGCs were preserved in PDTC-treated retinas 7 days post-transection compared to retinas in the control group. However, this kind of neuroprotective effect was not significant at 14 days post-transection. CONCLUSIONS: This study demonstrated that PDTC, mediated in part through the down-regulation of MMP-9, could contribute to delaying the death of RGCs following transection of the ON.