Whole Exome Sequencing in a Korean Child with Joubert Syndrome-related Disorders

Joubert syndrome and Joubert syndrome-related disorders (JSRDs) are rare autosomal recessive or X-linked disorders characterized by cerebellar vermis hypoplasia and a brain stem malformation, which presents as the “molar tooth sign” in magnetic resonance imaging (MRI). JSRDs are a group of clinically heterogeneous conditions that exhibit neurological manifestations and multiple organ involvement. JSRDs are also genetically heterogeneous, and approximately 20 causative genes that account for 45% of JSRDs have been identified. A 7-yr-old boy visited Wonkwang University Sanbon Hospital with the following presentations: no ocular fixation, ataxia, growth retardation, and hypotonia. Physical examination revealed facial dysmorphism, spindle shaped fingers, and height (99 cm) and weight (13 kg) below the third percentile. Ophthalmic examination revealed retinal dystrophy. A diagnosis of JSRDs was made based on clinical and brain MRI findings. We found two heterozygous variants c.2945 G>T; p.Arg982Met (G>T) and c.2216dupA; p.Phe740Valfs*2 (dupA) in AHI1, and a heterozygous c.3973C>T; p.Arg1325Trp (C>T) variant in KIF7 by whole exome sequencing (WES). Genetic analysis on the proband's father revealed that he had both AHI1 variants, but did not have the KIF7 variant, which was inconsistent with autosomal recessive inheritance. Therefore, the G>T variant and C>T variant were presumed to be of “uncertain significance.” Furthermore, one novel dupA variant was interpreted as “pathogenic,” while the second allele was not detected. Caution should be exercised while interpreting the significance of variants detected by WES. In addition, the involvement of genes other than the 20 known ones will require further investigation to elucidate the pathogenesis of JSRDs.

Prevention of UV-Induced Skin Damages by 11,14,17-Eicosatrienoic Acid in Hairless Mice In Vivo

Polyunsaturated fatty acids (PUFAs) are known to play important roles in various physiological and pathological processes. Recent studies have shown that some omega-3 (omega-3) PUFAs, such as eicosapentaenoic acid (EPA) and dodecahexaenoic acid (DHA), have protective effects on acute and chronic UV-induced changes. However, the effects of other omega-3 PUFAs including 11,14,17-eicosatrienoic acid (20:3) (ETA) on UV-induced skin damages are poorly understood. In this study, we investigated the cutaneous photoprotective effects of ETA in hairless mice in vivo. Female HR-1 hairless mice were topically treated with vehicle (ethanol:polyethylene glycol=30:70) only, 0.1% ETA, or 1% ETA once a day for 3 successive days after one time UV irradiation (200 mJ/cm2) on dorsal skins. Skin biopsy was carried out on the fourth day (72 hr after UV irradiation). We found that topical treatment with ETA attenuated UV-induced epidermal and dermal thickness and infiltration of inflammatory cells, and impairment of skin barrier function. In addition, ETA suppressed the expression of IL-1beta, COX-2, and MMP-13 induced by UV irradiation. Our results show that the topical application of ETA protects against UV-induced skin damage in hairless mice and suggest that ETA can be a potential agent for preventing and/or treating UV-induced inflammation and photoaging.

An fMRI Study Regarding the 'Theory of Mind' in Korean Schizophrenic Patients Using a First Order False Belief Task / 신경정신의학

OBJECTIVES: The aim of this study was to investigate brain activation during a Korean language-based 'theory of mind (TOM)' task and fMRI in Korean schizophrenic patients. METHODS: Fourteen Korean schizophrenic patients and 15 normal controls participated in this study. For all participants, several clinical states and psychosocial functions were evaluated. The subjects were then scanned while performing Korean language-based fMRI tasks. The tasks were comprised of conditions-first order false belief (TOM task), physical causality, and unrelated situations. Imaging data were analyzed using SPM2 software (uncorrected p<0.005, extent threshold kappa=10). RESULTS: 1) Compared with the control group, the patient group showed significantly poorer performance on the TOM task, and no significant correlation between TOM and empathic abilitiesy. 2) In the patient group, there were no significantly activated brain regions associated with the TOM task as compared to the physical causality task. With respect to between-group differences, the patient group showed significantly less activation of the left medial frontal region (primarily BA 8) and signifcantly different activation of the left precuneus (BA 7) associated with the TOM task. CONCLUSION: These results suggest that Korean schizophreniac patients show different brain activity associated with TOM functions, especially with respect to the Korean language-based first order false belief tasks.

The Difference of Neural Activity in Viewing between one's own Emotional Situation and Other's: A Neuroimaging Study about Perspective-Taking

OBJECTIVES: This study aimed to investigate the difference of brain activities in viewing a common emotional situation according to perspective-taking. METHODS: Using fMRI, brain activities were measured while performing the task viewing a common emotional situation on either self-perspective or third-person perspective in fourteen healthy men. The relatively activated brain areas on each perspective were investigated, then the relationship between the activated brain regions and the scores of self report about some emotion or empathic ability were explored. RESULTS: The relatively activated brain areas on self-perspective were bilateral paracentral lobule(BA 5), right postcentral gyrus(BA 3), right precentral gyrus(BA 4), left superior temporal gyrus(BA 22), left medial frontal gyrus(BA 6), whereas on third-person perspective right inferior frontal gyrus(BA 47), left caudate body and tail, right superior temporal gyrus(BA 38), right medial frontal gyrus(BA 8) were activated. The relative activity of left superior temporal gyrus on self-perspective was positively correlated with the score of Beck Depression Inventory. CONCLUSION: This study demonstrated that the activated brain region according to perspective-taking were different while viewing a common emotional situation. The depressive feeling would have an influence on the brain activity related to perspective-taking.

Long-term Visual Outcome of Arteriovenous Adventitial Sheathotomy on Branch Retinal Vein Occlusion Induced Macular Edema

PURPOSE: To evaluate long-term visual outcome of arteriovenous adventitial sheathotomy in BRVO-induced macular edema. METHODS: The visual outcomes of 8 patients following vitrectomy with arteriovenous adventitial sheathotomy for BVO-induced macular edema (surgery group) were retrospectively evaluated. The three-year post-operative visual acuity of the surgery group was compared with that of the conservatively managed controls. RESULTS: All patients were followed for a minimum of 36 months. Mean BCVA (logMAR) in the surgery group changed from 1.10+/-0.34 to 1.19+/-0.70 and to 0.80+/-0.36 at 12 and 36 months, respectively (p=0.959 at 12 months, p=0.018 at 36 months). In the control group, visual acuity improved from 1.15+/-0.43 to 0.43+/-0.44 and to 0.43+/-0.39 at 12 and 36 months, respectively (p=0.015 at 12 months, at p=0.003 at 36 months). A strong trend toward better visual acuity at 12 months and final examination was observed for controls. (surgery vs. control group, p=0.052 at 12 months, p=0.066 at 36 months). CONCLUSIONS: Considering the favorable natural course of BVO and the unproven effect of reperfusion on macular edema, surgical efficacy of arteriovenous adventitial sheathotomy requires further evaluation.

Intravitreal Triamcinolone Injection with or Without Bevacizumab for Diabetic Macular Edema

PURPOSE: To compare the effect of intravitreal triamcinolone injection with and without bevacizumab for diabetic macular edema. METHODS: Of 69 patients (69 eyes) diagnosed with diabetic macular edema without any history of other intraocular disease or intraocular operation, 45 eyes (45 patients) were injected with intravitreal triamcinolone (4 mg) and the remaining eyes (24 patients) were injected with triamcinolone (2 mg) and bevacizumab (1.25 mg). The visual acuity and central macular thickness of treated eyes from both groups was measured using OCT, and these measurements were compared between the two groups. RESULTS: There were no statistical differences between the two groups with respect to baseline data. Central macular thickness (CMT) was reduced in both groups, and BCVA improved in both groups. No significant differences were detected in changes in CMT or BCVA between the two groups. CONCLUSIONS: Intravitreal injection of triamcinolone had a beneficial effect on DME in terms of CMT reduction and BCVA improvement. Addition of three consecutive intravitreal bevacizumab injections, however, did not show any significant addictive effect during the follow-up period.

Intravitreal versus Posterior Subtenon Injection of Triamcinolone Acetonide for Diabetic Macular Edema

PURPOSE: To compare the short-term effects of intravitreal versus posterior subtenon injection of triamcinolone acetonide for diabetic macular edema. METHODS: This is a prospective and interventional study. Sixty eyes of 60 patients who had diffuse diabetic macular edema were assigned to receive a single intravitreal injection (4 mg) or a single posterior subtenon injection (40 mg) of triamcinolone acetonide. The central retinal thickness was measured using optical coherent tomography before injection and at 1 and 3 months after injection. Visual acuity and intraocular pressure (IOP) were also measured. RESULTS: Both intravitreal and posterior subtenon injections of triamcinolone acetonide resulted in significant improvements in visual acuity at 1 month and 3 months after injection. Both groups resulted in a significant decrease in central macular thickness (CMT) at 1 month and 3 months post-injection. IOP in the intravitreal injection group was significantly higher than in the posterior subtenon injection group at 3 months after injection. CONCLUSIONS: The posterior subtenon injection of triamcinolone acetonide had a comparable effect to the intravitreal triamcinolone injection and showed a lower risk of elevated IOP. Posterior subtenon injection of triamcinolone acetonide may be a good alternative for the treatment of diffuse diabetic macular edema.

Bilateral Duane's Retraction Syndrome Treated with Bilateral Horizontal Transposition of Vertical Recti

PURPOSE: To report a male infant with bilateral Duane's retraction syndrome treated with bilateral horizontal transpositions of vertical recti to the lateral rectus muscle. METHODS: An 8-month-old boy showed bilateral Duane's retraction syndrome with esotropia of 45PD, severe limitation of abduction (-4 and -3.5 in each eye) and mild globe retraction in both eyes. It was assumed that he inherited the condition from his father through an autosomal dominant pattern. His father showed esotropia of 25PD with -4 limitation of abduction in the left eye and a left head-turn of 10 degrees. He also had +2 globe retraction, +1 upshoot and +2 downshoot in adduction of the left eye. Transposition of two vertical recti to the lateral rectus muscle was performed in both eyes of the boy. RESULTS: Nine months after surgery, the boy had achieved a microesotropia of 6PD in primary gaze with stereopsis of 3000 seconds of arc and considerable improvement in abduction (-2, -1.5 in each eye). The amount of correction of esodeviation was 39PD. This favorable state was maintained at follow-up 3.5 years after surgery. CONCLUSIONS: An 8-month-old boy who had esotropia of 45PD caused by bilateral Duane's retraction syndrome, underwent bilateral horizontal transpositions of vertical recti to the lateral rectus muscle. He achieved a microesotropia of 6PD in primary gaze and considerable improvement of abduction with only mild eyeball retraction.

The Effect of Posterior Vitreous Detachment on Macular Edema in Branch Retinal Vein Occlusion

PURPOSE: To quantitatively compare the role of posterior vitreous detachment in macular edema associated with branch retinal vein occlusion (BRVO) using OCT. METHODS: A retrospective study of 36 eyes with BRVO-associated macular edema was carried out from November 2003 to February 2005. There was posterior vitreous detachment (PVD) in 23 eyes [PVD (+) group], and vitreoretinal attachment on the fovea in 31 eyes [PVD (-) group]. PVD was detected with an indirect ophthalmoscope or 90D lens. The foveal thicknesses of the two groups were measured and compared. RESULTS: The mean foveal thicknesses of the PVD (-) and PVD (+) groups were 398.0+/-217.2 micrometer and 233.6+/-80.6 micrometer, respectively (p=0.000, Mann-Whitney test). The mean BCVA (log MAR) was 0.77+/-0.52 in the PVD (-) group and 0.40+/-0.37 in the PVD (+) group (p=0.002, Mann-Whitney test). CONCLUSIONS: The extent of macular edema associated with BRVO was significantly less in the PVD(+) group and BCVA was significantly better in the PVD (+) group as well.

A Case of Cancer-Associated Retinopathy with Small Cell Lung Cancer

PURPOSE: To report a case of cancer-associated retinopathy developed in a patient with small cell lung cancer, which is a kind of paraneoplastic syndrome. METHODS: A 78-year-old woman presented complaining of decreased visual acuity and visual field that had developed about 15 days previously. She was diagnosed with small cell lung cancer 1.5 years ago and underwent 3 cycles of chemotherapy. At presentation, the best-corrected visual acuity was hand motion in both eyes and there was no afferent pupillary defect. Slit-lamp biomicroscopic examination revealed no specific abnormality in the anterior segment of either eye, and intraocular pressure was normal. Posterior segment examination demonstrated remarkable arteriolar narrowing in both eyes, but there was little doubt about the presence of an optic nerve lesion such as optic disc edema or pallor. RESULTS: Fluorescein angiography and brain magnetic resonance imaging (MRI) revealed no significant abnormalities. However, electroretinograms (ERG) demonstrated marked reduction in the a and b waves. Visual evoked response was delayed for the latency period. She was treated with systemic steroid, after which her visual acuity gradually improved.

Diurnal Variation of Macular Thickness in Diabetic Macular Edema

PURPOSE: To evaluate the diurnal variation of macular thickness in eyes with diabetic macular edema. METHODS: We measured macular thickness using optical coherence tomography in 33 eyes with diabetic macular edema and 33 normal control eyes at 7 am, 11 am, 2 pm, and 5 pm. We investigated the correlation between macular thickness change and several factors such as sex, duration of diabetes mellitus, presence of hypertension, HbA1c, creatinine clearance, blood urea nitrogen, serum creatinine, blood sugar, blood pressure, severity of diabetic retinopathy, and whether PRP was done or not. RESULTS: Retinal thickness in 3.45 mm macular area was the thickest at 7 am and then decreased over the day to be thinnest at 5 pm (p

Comparison of Results between Two Methods in Removal of Lacrimal Sac Medial Wall in Endoscopic Dacryocystorhinostomy

PURPOSE: To compare the surgical results between Nd: YAG laser and sickle knife, as instruments for removal of the medial wall of the lacrimal sac at the time of endoscopic dacryocystorhinostomy (DCR). METHODS: From June 2001 to January 2002, 70 patients with nasolacrimal duct obstruction were arbitrarily divided into two groups. One group underwent endoscopic DCR using sickle knife (sickle knife group) and the other group underwent endoscopic DCR using Nd: YAG laser (laser group). We evaluated the duration of wound healing, complications, and success rates. RESULTS: The duration of wound healing in the sickle knife and laser groups was 3.6 +/- 0.6 weeks and 4.0 +/- 0.3 weeks, respectively (p=0.09). Granuloma formation was statistically different between the sickle knife (45.7%, 16/35) and laser (22.9%, 8/35) groups (p=0.04). There were no significant statistical differences in the membranous obstruction rate, common canalicular obstruction rate, or synechiae formation rate between the two groups. The success rate at postoperative 1 year was 82.9% (29/35) in the sickle knife group and 88.6% (31/35) in the laser group (p=0.49). CONCLUSIONS: The laser group obtained the higher success rate and lower incidence of granuloma formation at the internal ostium than the sickle knife group. Wound healing seemed to be faster in the sickle knife group but showed higher granuloma formation in the sickle knife group. This might suggest that the instrument used in the removal of the medial wall of the lacrimal sac could influence the duration of wound healing as well as granuloma formation at the internal ostium.

The Clinical Outcome of Endoscopic Transnasal Conjunctivodacryocystorhinostomy Using MEDPOR(R) Coated Tear Drain

PURPOSE: Tube displacement, consisting of protrusion, spontaneous loss, and intrusion, is the most common cause of failure in conjunctivodacryocystorhinostomy with Jones tube. Recently, MEDPOR(R) Coated Tear Drain was designed to minimize these complications. We evaluate the surgical outcome of conjunctivodacryocystorhinostomy with MEDPOR(R) Coated Tear Drain. METHODS: Primary conjunctivodacryocystorhinostomy or revision surgery using MEDPOR(R) Coated Tear Drain was done on 23 eyes of 23 patients and the development of displacement was monitored. Thirteen patients suffered from habitual displacement of Jones tube and underwent revision surgery, while the remaining 10 underwent primary conjunctivodacryocystorhinostomy. RESULTS: During 12-month follow-up after surgery, tube intrusion was noted in one among the 23 patients. Protrusion or spontaneous loss of tube did not develop. CONCLUSIONS: The use of MEDPOR(R) Coated Tear Drain may be very effective not only for revision surgery in patients who have suffered from habitual displacement of Jones tube but also on primary conjunctivodacryocystorhinostomy.

Atypical Vogt-Koyanagi-Harada Syndrome in a 7-Year-Old Boy

PURPOSE: Vogt-Koyanagi-Harada syndrome is more common in adults than in children. We report a atypical case of Vogt-Koyanagi-Harada syndrome like white dot syndromes in a 7-year-old child. METHODS: A 7-year-old child visited with complaints of decreased binocular visual acuity. Under ophthalmologic examination, anterior uveitis and optic neuropathy were found. But there was no other retinal lesion. After high-dose intravenous corticosteroids pulse therapy, yellow pigment lesions like white dot syndromes developed in peripheral retina and enlarged without serous retinal detachment. RESULTS: In 5 months after high-dose intravenous corticosteroids pulse therapy, anterior inflammation was decreased and visual acuity was 0.8 in both eyes. But depigmented retinal lesions were increased and sunset glow occurred. Alopecia and poliosis of hair were found. Human leukocyte antigen typings revealed HLA-DR4 antigen.