Principais achados em um paciente com diagnóstico de Amaurose Congênita de Leber / Main findings in a patient diagnosed with Leber's Congenital Amaurosis

RESUMO A amaurose congênita de Leber, também conhecida como neuropatia óptica hereditária de Leber, é caracterizada por uma das formas mais graves de distrofia da retina com início na infância. Os achados clássicos são deficiência visual grave e precoce, nistagmo e eletrorretinograma (ERG) anormal ou não detectável. O objetivo deste estudo é relatar um caso de um paciente com amaurose congênita de Leber com comprometimento visual desde os 6 meses de vida e acentuado declínio visual a partir dos 15 anos de idade. A realização de exames específicos para confirmar o diagnóstico é importante para o manejo e o seguimento adequado do paciente e para proporcionar melhor qualidade de vida para o mesmo.

ABSTRACT Leber Congenital Amaurosis, also known as Leber hereditary optic neuropathy, is characterized by one of the most severe forms of childhood-onset retinal dystrophy. Classic findings are severe and early visual impairment, nystagmus, and abnormal or undetectable electroretinogram. The aim of this study is to report a case of a patient with Leber Congenital Amaurosis with visual impairment since the first six months of age and marked visual decline from fifteen years of age. Performing specific tests to confirm the diagnosis is important for the proper management and follow-up of the patient and to provide them with a better quality of life.

Phenotypic analysis of patients with Leber congenital amaurosis caused by new gene mutations / 中华眼底病杂志

Objective:To identify 3 the disease-causing genes and mutations of Leber congenital amaurosis (LCA), and to study the correlation of phenotype and genotype.Methods:A retrospective study. Four LCA patients and seven family members who were diagnosed by eye examination in Ning Xia Eye Hospital of People's Hospital of Ningxia Hui Autonomous Region from January to December 2021 were included in the study. Four patients were from 3 unrelated families. Detailed collection of medical history and family history were received. Related ophthalmologic examination were collected and genomic DNA was extracted from peripheral blood. Whole-exome sequencing method was used for genetic diagnosis. The identified variant was confirmed with Sanger sequencing. Potential pathogenic mutation was analyzed using software and conserved domain analysis and performed co-separated analysis between the family member and the proband.Results:Of the 4 patients, 1 patient was males and 3 patients were females; the age was from 4 to 18 years. Nystagmus were seen in 3 cases, finger pressing eyes and night blindness was seen in 1 cases; electroretinogram showed 4 cases of extinction or near extinction. The foveal reflection was visible in all eyes, and there was no obvious abnormality in the peripheral retina. One eye had strong reflection signal with raised ellipsoid in macular area; two eyes had weak reflection signal faintly visible between retinal layers; 1 eye had increased blood vessel branches, peripheral retinal non-perfusion area with capillary leakage; annular strong autofluorescence in macular area 4 eyes. No obvious abnormality was found in the phenotypes of family members. Genetic testing showed that the proband of pedigree 1 (Ⅱ-1) was found a homozygous missense mutation in c.640A>T (p.C214S) (M1) of PRPH2 gene. The proband of pedigree 2 (Ⅱ-2) was found compound heterozygous mutation in c.1256G>A(p.R419Q) (M2) and c.1A>C (p.M1L) (M3) of TULP1 gene. The proband 3 (Ⅱ-1) and her sister (Ⅱ-2) were both found compound heterozygous mutation in c.1943T>C (p.L648P) (M4) and c.380C>T (p.P127L) (M5) of GUCY2D gene. The parents and sister (Ⅱ-1) of the proband in family 2 and the parents of the proband in family 3 were all carriers of the corresponding heterozygous variant. M1, M3, M4, M5 were novel mutations and unreported. The genotype and disease phenotype were co-segregated within the family. According to the analysis of pedigree and genetic testing results, all 3 families were autosomal recessive inheritance. The amino acid conservation analysis found that M1, M2, M3, M4, and M5 were highly conserved among species. The results of bioinformatics analysis were all pathogenic variants. Conclusions:PRPH2 gene M1, TULP1 gene M3, and GUCY2D gene M4, M5 were novel mutations and not been reported in the literature and database. This research expanded the gene mutation spectrum of LCA. The patients with LCA have available characterristics, including onset age, varying ocular fundus and severe visual impairment.

Comprehensive analysis of pathogenic genes and clinical phenotypes in patients with Leber congenital amuarosis / 中华眼底病杂志

Objective:To observe clinical phenotypes and analyze the pathogenic genes of Leber congenital amaurosis (LCA).Methods:A retrospective clinical study. From 2019 to 2020, 2 patients diagnosed with LCA by genetic testing in Tianjin Medical University Eye Hospital and their 6 unaffected family members were enrolled in the study. Two patients were from 2 unrelated families, both were probands. The patient's medical history was inquired in detail, slit lamp microscopy, ultra-widefield fundus photography, autofluorescence, and flash visual evoked potential (F-VEP) were performed. Peripheral vein blood (3-5 ml) was collected and genomic DNA was extracted from all study subjects. A total of 381 pathogetic genes associated with inherited retinal diseases, were selected by targeted exome sequencing capture strategy. Sanger sequencing was used to verify suspected pathogenic mutations. Candidate pathogenic mutations were identified after bioinformatics analysis. Sanger sequencing, real-time quantitative polymerase chain reaction and family co-identification were used to confirm the final mutations.Results:Two patients were male, aged 3 and 27 years. One case had vision loss in both eyes, accompanied by nystagmus and acupressure eye sign since childhood. The clinical hallmark of the proband (F1-Ⅱ-3) in F1 includes clearly boundary of optic disc, normal retinal blood vessels and macular fovea. The implied period of the maximum forward wave in both eyes of F-VEP was roughly normal, and its amplitude decreased significantly. The phenotype of the proband (F2-Ⅱ-1) in F2 includes optic nerve head pallor, bone-spicule intraretinal pigmentation, "gold-foil maculopathy" , retina patchy hypo-autofluorescence in both eyes. There was no abnormal phenotype in the eyes of the family members. According to the genetic diagnosis, the proband (F1-Ⅱ-3) carried the GUCY2D gene c.835G>A (p.D279N) (M1) and exon 9-19 deletion (M2) compound heterozygous mutations, in which M1 was derived from healthy mother and M2 was derived from healthy father. The proband (F2-Ⅱ-1) carried CRB1 gene c.1576C>T(R526X) (M3) and c.1522T>C (C508R) (M4) compound heterozygous mutations, in which M3 from the healthy father, M4 from the healthy mother. M2 and M4 were novel mutations. Conclusion:GUCY2D gene mutations lead to LCA1 type in the F1 family, CRB1 gene mutations lead to LCA8 type in the F2 family; there are significant different phenotypes caused by different pathogenic genes.

Avaliação do Setor de Baixa Visão de pacientes gemelares com distrofia retiniana / Low vision center evaluation of twin patients with retinal dystrophy

Resumo É relatado o caso de duas pacientes gemelares idênticas do sexo feminino portadoras de distrofia retiniana em investigação. A principal hipótese diagnóstica é a amaurose congenita de leber. Foi realizada avaliação pelo setor de visão subnormal em centro oftalmológico, com orientação de uso de recursos ópticos e não ópticos para melhoria principalmente das relações socioeducativas das pacientes.

Abstract In this paper, we report a two identical female twin patients with retinal distrophy in investigation. The main diagnostic hypothesis is the leber congenital amaurosis. The patients were evaluated by the Low Vision Center at the Hospital Oftalmologico de Sorocaba, São Paulo-Brazil, using optical and non-optical resources for mainly patient's socio-educational relationship improvement.

Progress in research on LCA2 gene therapy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Leber's congenital amaurosis(LCA)is a genetic eye disease that can cause blindness. Infants with LCA may have a severe low vision or loss of vision at the early stage. The LCA2 type of this disease is related to RPE65 mutation. According to previous studies, there is no effective treatment for genetic retinal diseases including LCA2. In recent years, with the advances in gene therapy technology, great progress in the treatment of genetic retinal diseases has been made, among which the most successful one is the gene therapy of LCA2. This paper briefly introduces the development of the gene therapy of LCA2, and reviews the correlation between age and injection type, dosage, injection method, measuring method as well as therapeutic effect and the stability of therapeutic effect in previous clinic trials, which provides reference and clinical treatment experience for the clinical application of the gene therapy of LCA2 in China.

Amaurosis and contralateral cranial nerve pairs III and VI paralysis after peribulbar block - Case report / Amaurose e paralisia do III e do VI pares cranianos contralaterais após bloqueio peribulbar - relato de caso

Abstract Background and objectives: Peribulbar anesthesia has emerged as a safer option compared with intraconal retrobulbar block. Still, peribulbar anesthesia may not be considered without risk. Numerous complications have been described when performing this technique. This report aims to describe a rare case of amaurosis and contralateral paralysis while attempting to perform a peribulbar anesthesia. Case report: Male patient, 75-year old, physical status ASA II, undergoing cataract surgery by phacoemulsification with intraocular lens implantation. Sedated with fentanyl and midazolam and subjected to peribulbar anesthesia. There were no complications during surgery. After finishing the procedure, the patient reported lack of vision in the contralateral eye. Akinesia of the muscles innervated by the cranial nerve pairs III and VI, ptosis, and medium-sized pupils unresponsive to light stimulus were observed. Four hours after anesthesia, complete recovery of vision and eyelid and eyeball movements was seen in the non-operated eye. Conclusions: During peribulbar anesthesia, structures located in the intraconal space can be accidentally hit leading to complications such as described in the above report. Following the technical guidelines and using appropriate size needles may reduce the risk of such complication, but not completely.

Resumo Justificativa e objetivos: A anestesia peribulbar surgiu como uma opção mais segura quando comparada com o bloqueio retrobulbar intraconal. Ainda assim, a anestesia peribulbar não pode ser considerada isenta de riscos. Inúmeras complicações foram descritas quando da aplicação dessa técnica. O presente relato tem como objetivo descrever um caso raro caracterizado por amaurose e paralisia contralaterais quando da tentativa de se fazer a anestesia peribulbar. Relato de caso: Paciente masculino, 75 anos, estado físico ASA II, submetido à facectomia por facoemulsificação com implante de lente intraocular. Sedado com fentanil e midazolam e submetido a APB. Não houve intercorrências durante a cirurgia. Após o término do procedimento o paciente relatou ausência de visão no olho contralateral. Foram observadas acinesia da musculatura inervada pelo III e VI pares cranianos, ptose palpebral e pupilas de tamanho médio, não responsivas ao estímulo luminoso. Após quatro horas da anestesia, houve recuperação completa da visão, da movimentação das pálpebras e do globo ocular não operado. Conclusões: Durante a APB, estruturas localizadas no espaço intraconal podem ser atingidas acidentalmente levando a complicações como a descrita no relato acima. O respeito às diretrizes técnicas e o uso de agulhas com o tamanho adequado podem reduzir o risco de tal complicação, mas não de forma completa.

Compound heterozygous mutations of CRB1 gene in a Chinese family with Leber congenital amaurosis by whole exome sequencing / 中华实验眼科杂志

Objective To investigate the disease-causing mutation in a family with Leber congenital amaurosis (LCA).Methods A Chinese Han pedigree with LCA from Chaoshan area was recruited in Shantou International Eye Center in August 2011.The clinical features of the families were evaluated,including medical history,best corrected visual acuity,intraocular pressure and fundus photography.The peripheral blood sample of 5 ml was collected from each of the family members for the extraction of genomic DNA.DNA of the proband was investigated by whole exome sequencing (WES) and was filtered for function of variants and inheritance pattern.Then,Sanger sequencing was performed to confirm the WES result on all the participating subjects in the pedigree.Results There were 11 families of 3 generations in this pedigree,and 2 female LCA patients were found (Ⅱ 2 and Ⅱ4) who were sisters.The parents (Ⅰ-1 and Ⅰ-2) and children (Ⅲ-1,Ⅲ-2,Ⅲ-3 and Ⅲ-4) of the patients showed normal phenotype,suggesting an autosomal recessive pattern.The patients appeared severe visual impairment during early childhood.Ophthalmic examination showed diffuse pigmentation on the retina and attenuation of retinal artery in both patients.WES of proband revealed two compound heterozygous mutations (c.2234C ＞T,p.T745M;c.3488G＞T,p.C1163F) of the CRB1 gene.Sanger sequencing confirmed the mutations in both patients (Ⅱ-2 and Ⅲ-4),and the parents of the patients were found to carry one mutations respectively and the other subjects with normal phenotype had neither none or only one mutation.Conclusions The compound heterozygous mutation of c.2234C＞ T,p.T745M and c.3488G＞T,p.C1163F in CRB1 is responsible for LCA pathogenesis this Chinese Han pedigree.

Changes of serum lipids in patients with Leber congenital amaurosis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the serum lipids changes in patients with Leber congenital amaurosis(LCA).<p>METHODS: Based on the retrospective study and the simple size in the statistics, 50 cases of LCA patients and 52 cases of normal people were included. The serum levels of low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), triglycerides(TG), and total cholesterol(TC)were measured by professionals in hospital according to the single blind study. Data were analyzed statistically between the LCA group and normal group. <p>RESULTS: Among the 50 patients with LCA, abnormal serum lipid content accounted for 46%, of which 26% were low in HDL-C levels, hypertriglyceridemia accounted for 48%, hypercholesteremia accounted for 17%, respectively, 9% of patients had mixed hyperlipidaemia. The serum level of HDL-C was 1.221±0.317mmol/L in the LCA group, which was significantly lower than the normal group(<i>P</i><0.05). The serum levels of TG and TC were 1.377±1.171mmol/L and 4.506±0.694mmol/Lin the LCA group, which were significantly higher than the normal group(all <i>P</i><0.01). There was no significant difference in the serum level of LDL-C between LCA and normal group(<i>P</i>>0.05). <p>CONCLUSION: In patients with LCA, abnormal concentration changes of HDL-C,TG and TC may be associated with the occurrence of LCA.

Charles Miller Fisher: the 65th anniversary of the publication of his groundbreaking study "Transient Monocular Blindness Associated with Hemiplegia" / Charles Miller Fisher: 65 anos da publicação de seu estudo inovador "Cegueira monocular transitória associada com hemiplegia"

ABSTRACT Charles Miller Fisher is considered the father of modern vascular neurology and one of the giants of neurology in the 20th century. This historical review emphasizes Prof. Fisher's magnificent contribution to vascular neurology and celebrates the 65th anniversary of the publication of his groundbreaking study, "Transient Monocular Blindness Associated with Hemiplegia."

RESUMO Charles Miller Fisher é considerado o pai da neurologia vascular moderna, e um dos gigantes da neurologia no século XX. Esta revisão histórica enfatiza a magnífica contribuição de Miller Fisher na neurologia vascular, particularmente com a celebração dos 65 anos de publicação do seu estudo inovador intitulado "Cegueira monocular transitória associada com hemiplegia".

Degeneration of short-wavelength cone cells in rd12 mice / 中华实验眼科杂志

Background Retinitis pigmentosa (RP) is one of the causes of congenital blindness.It is well known that the degeneration process of rod cells is difficult to detect in RP.Retinal degeneration 12 (rd12) mice is a new,spontaneously arising mouse model for human Leber congenital amaurosis (LCA),and it is helpful for us to explore the pathogenesis and determine the treating target of RP.Objective This study was to investigate the natural disease process of short-length sensitive cone cells in rd12 mice,a LCA Rpe65rd12 (B6 [A]-Rpe65rd12/J) mouse.Methods The rd12 mice at postnatal (P) 14,P21,P35 and P90 were selected (5 mice for each),and the wild-type C57BL/6J (B6) mice with matched ages were included as controls.Photopic full-field electroretinogram (ERG) was recorded with Roland Q450SC UV visual physiology instrument.Cone response was recorded using single white light-emitting diode (LED) stimulation with the flash intensity of 1.00 cds/m2 and 1.96 cds/m2,and short wave-length sensitive cone response was recorded using ultraviolet light ([363 ±6] nm) stimulation with the flash intensity of 2.0 mWs/m2 and 3.0 mW/m2.The mice were sacrificed and retinal whole-mounts were prepared.The distribution and number of cone cells and UV-sensitive cone cells were detected by FITC-peanut agglutinin (FITC-PNA) and Cy3 immunofluorescence stainning,respectively.Results In P14 rd12 mice,the ERG responses of overall cone cells presented the negative waveform and the latency was delayed,and UV-sensitive cone response was unrecordable.The b-wave amplitude of overall cone cells reduced by 75％ in P21 rd12 mice compared with wild-type B6 mice,and the mean latency of b-wave in the P21 rd12 mice was significantly longer than that in the wild-type B6 mice ([102.80± 11.39] ms vs.[43.40± 5.60] ms) (t =-8.106,P =0.001).The mean b-wave amplitudes of U Vsensitive cone cells were (59.60± 36.00),(82.40± 12.22) and (68.43 ± 17.63) μV in the wild-type B6 mice,andthose in the rd12 mice were unrecordable.Immunofluorescence showed that a lager number of cone cells with green fluorescence were seen,and the expression of opsin with red fluorescence was displayed in the UV-sensitive cone cells of nasal lateral on retinal ventral side in P14 wild-type B6 mice;while only a few opsin positive-response cells were seen in P14,P21 and P35 rd12 mice.Conclusions In rd12 mice,the functional abnormality and quantitative reduction of cone cells appear in the early postnatal days,and the loss of UV-sensitive cone cells is earlier and more obvious.

Abnormalities of the five serum ions in patients with Leber congenital amaurosis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To study the concentration changes of the serum magnesium, calcium, potassium, sodium and chloride ions of the patients of Leber congenital amaurosis(LCA).<p>METHODS:Based on the retrospective study and the simple size in the statistics, 50 cases of LCA patients and 99 cases of normal people were tested the serum ions by professionals in hospital according to the single blind study. Data were analyzed statistically between LCA and normal groups. <p>RESULTS: In the clinical serum ions test of LCA group, the concentration of calcium and potassium were 2.338±0.090mmol/L and 4.164±0.356mmol/L respectively, which were significantly higher than those of the normal group(all <i>P</i><0.05), but the concentration of magnesium was 0.835±0.059mmol/L, which was significantly lower than the normal group(<i>P</i><0.05). There were no significantly differences in remainder two serum ions concentration of LCA groups,comparing with the normal group(all <i>P</i>>0.05). <p>CONCLUSION: In the patients with LCA, abnormal concentration changes of magnesium, calcium and potassium will be needed to concern of the ophthalmologist, which is probably related with the occurrence of LCA.

Amaurosis Fugax Associated with Ipsilateral Internal Carotid Artery Agenesis

PURPOSE: We report a case of amaurosis fugax associated with ipsilateral internal carotid artery agenesis. CASE SUMMARY: A 50-year-old woman presented with amaurosis fugax in her left eye; the frequency of episodes of the condition had recently increased to once a month. She had a history of hypertension and dyslipidemia, and was under medical therapy. The visual acuity of both eyes was 20/20. Slit-lamp examination was normal except for pseudophakia. Ophthalmoscopy revealed a myopic tigroid fundus and a myopic tilted disc. No abnormalities were evident in fluorescein fundus angiography. Brain computed tomography showed that the left bony carotid canal was absent, and magnetic resonance angiography showed that the left internal carotid artery was also absent. She was diagnosed with left internal carotid artery agenesis. Other neurological and hematological parameters were within normal ranges. The amaurosis fugax spontaneously disappeared and has not recurred over the past 12 months. Our case, although rare, suggests that amaurosis fugax may be associated with internal carotid artery agenesis.

Sospecha clínica y tratamiento quirúrgico de los mucoceles esfenoidales / Diagnosis and surgical treatment of sphenoid mucoceles

Introducción: Los mucoceles son formaciones benignas de lento crecimiento que pueden aparecer en cualquier seno paranasal, representando el seno esfenoidal menos del 10%. Objetivo: Presentamos nuestra experiencia de mucoceles en el seno esfenoidal. Material y método: Se obtuvieron los datos a partir de nuestra base de datos que recoge prospectivamente los casos de tumores de cabeza y cuello. Entre enero 1989 y enero 2013 se registraron 58 mucoceles en 54 pacientes, de los cuales 4 (7%) eran de seno esfenoidal. Tres pacientes eran mujeres y uno varón, con edades comprendidas entre 42 y 61 años. Todas las lesiones fueron estudiadas con endoscopia nasal, tomo-grafía computarizada y resonancia magnética. Resultados: Tres pacientes presentaron un antecedente quirúrgico de seno paranasal. El síntoma más frecuente fue la cefalea (3 pacientes de 4). Dos pacientes presentaron diplopia y uno pérdida progresiva de agudeza visual, requiriendo manejo quirúrgico urgente. Todos fueron tratados con esfenoidotomía por abordaje endoscópico endonasal. Fueron dados de alta a las 48 h posteriores con antibioticoterapia. Ninguno presentó recidiva. Conclusión: Los mucoceles esfenoidales representan menos del 10% de los mucoceles nasosinusales. La pérdida de agudeza visual requiere un rápido diagnóstico y manejo terapéutico quirúrgico urgente. El tratamiento de elección es la marsupialización.

Introduction: Sinus mucoceles are benign cysts that may appear in any sinus, but only 1%-10% occur in the sphenoid sinus. Aim: We describe the cases of sphenoid sinus mucoceles seen at our centre over the last 25 years. Material and method: In a prospective review of all mucoceles diagnosed between 1989 and 2013, we identified 58 mucocels in 54 patients. Four of the 58 (7%) were sphenoid mucoceles. There were three female patients and one male, and ages ranged from 42 to 61 years. We performed an endoscopy, CT and MR in all patients to confirm diagnosis. Results: Three patients had had endoscopic endonasal surgery in the past. The presenting symptoms were headache in 3 patients, diplopia in two, and visual loss, causing blindness, in one. The patient with amaurosis requiered urgent surgery. All four patients underwent sphenoidotomy with marsupialisation by the endonasal endoscopic approach. They were discharged 48 hours later on oral antibiotics. No recurrences have been observed to date. Conclusions: Sphenoid mucocele is a rare disease, requiring prompt treatment in cases of amaurosis. Good results can be achieved with endonasal endoscopic marsupialisation.

Ocular and Systemic Manifestation of Amaurosis Fugax: Six-Year Observational Study

PURPOSE: To investigate the prevalence of ocular and systemic disease causing amaurosis fugax and to discuss the ocular and systemic manifestation of each disease. METHODS: Consecutive patients who had amaurosis fugax were retrospectively studied from 2007 to 2013. Carotid evaluation using Doppler was performed in all patients. Ocular and medical histories were taken and bilateral ophthalmic evaluation performed. RESULTS: This study included 35 patients. The mean age of patients was 63 years and 27 patients were male; 29 unilateral and 6 bilateral eyes were involved. Associated systemic disease included hypertension (54.3%) and diabetes mellitus (34.2%). The most frequent cause of amaurosis fugax was retinal artery occlusion (28.6%) followed by ocular ischemic syndrome (22.9%), other vascular diseases (11.4%), and retinal vein occlusion (5.7%). The remaining 31.4% patients with amaurosis fugax had no vascular disease. Clinically significant stenosis of the internal carotid artery was observed in 16 patients (45.7%) and 6 of these patients (37.5%) had retinal artery occlusion disease. CONCLUSIONS: Prevalence and clinical manifestation of amaurosis fugax is very complex. Patients with transient visual disturbance are at risk for retinal artery occlusion, ocular ischemic syndrome and other diseases which cause visual loss. Therefore, careful history taking and urgent systemic and ophthalmic evaluations should be performed.

Amaurosis congénita de Leber: Reporte de caso / Leber's congenital amaurosis: Case report

La amaurosis congénita de Leber es un desorden clínico, genético y heterogéneo caracterizado por una severa pérdida de la visión al nacimiento. Se presenta en un 10 a 18% de los casos de ceguera congénita. Algunos pacientes muestran solamente ceguera de origen retinal mostrando evidencia de un involucro multisistémico. En la presentación de este caso se hace la revisión bibliográfica del tema, la presentación de un caso clínico y se describe la importancia del manejo estomatológico de estos pacientes, ya que es importante el conocimiento y el entendimiento de la patología y de las consecuencias de su tratamiento.

Leber's congenital amaurosis is an heterogeneous and genetic clinical disorder characterized by severe loss of vision at birth. It accounts for 10 to 18% of congenital blindness cases. Some patients exhibit solely retinal blindness and show evidence of multi-systemic involvement. The presentation of this case includes bibliographic review of the subject, presentation of a clinical case and description of the importance of stomatologic handling of these patients. Knowledge and understanding of the disease as well as treatment sequels are paramount.

The research status of preclinical animal experiments of gene therapy for Leber congenital amaurosis / 中华实验眼科杂志

Leber congenital amaurosis (LCA) is extremely severe hereditary retinal dystrophy,because it leads to congenital bilateral blindness in early childhood.With the development of molecular genetics and the therapeutic gene replacement technology,gene therapy clinical trials have obtained exciting results on the basis of relatively satisfied with preliminary clinical experimental results by adeno-associated virus (AAV) vector-mediated gene therapy in the past decade.These researching methods include intravitreal injection and subretinal space injection of gene vector,and the investigating indexes include evaluations of visual function and safety,such as immune reaction of the animals,ocular histopathological change,complications and bio-distribution of gene sequence.The preliminary success of the LCAⅡ Ⅱ gene therapy will give some clues to the other inherited retinal diseases.This review focuses on the present status of pre-clinical animal experiments of its gene therapy.

Amaurosis cortical aguda secundaria a preeclampsia / Acute cortical blindness secondary to preeclampsia

La amaurosis cortical aguda es una complicación dramática y poco común de la preeclampsia. Se presenta un caso de paciente de 29 años con diagnóstico de preeclampsia grave quien describió deterioro de la agudeza visual repentino en el puerperio inmediato. El fondo de ojo fue normal. La paciente identificaba la luz intensa. Las pupilas estaban reactivas y no se observo la presencia de nistagmo. Se le realizó una resonancia magnética cuyos resultados fueron normales, por lo que se realizó el diagnóstico de amaurosis cortical aguda.

Acute cortical blindness is an uncommon and dramatic complication of preeclampsia. We present a case of a 29 years-old patient with diagnosis of severe preeclampsia who described a sudden loss of visual acuity during immediate puerperium. Fundi were normal. Pupils were reactive and there was no nystagmus A magnetic resonance were performed with normal results, because diagnosis of acute cortical blindness was done.

Current advance in genetics and clinical phenotype of Leber congenital amaurosis / 中华实验眼科杂志

Leber congenital amaurosis (LCA) is one of the main inherited retinal diseases causing congenital blindness.LCA is also characterized by genetic heterogeneity and variable clinical phenotypes.Recent years,a lot of molecular genetic studies related with its pathogenesis have been performed.So far,20 causative genes have been identified that account for LCA.Some correlations between genotype and clinical phenotype have also been found.Those specific clinical manifestations may help to identify the mutant gene that causes the LCA.This review summarized the causal genes,their roles in the pathogenesis of LCA,coupled with relationship between specific gene and Corresponding phenotype,which will assist the clinician in patient diagnosis and counseling.

Correct interpretation and evaluation of the results of clinical trials of gene therapy for Leber congenital amaurosis / 中华实验眼科杂志

The treatment of hereditary retinal disease is still one of the contemporary scientific problems.Leber congenital amaurosis (LCA) is one type of congenital retinal diseases.Desirable results have been achieved in ongoing clinical trials of gene therapy for LCA,and the efficacy and safety in the intraocular injection of a gene inserted in an adeno-associated virus (AAV) have been verified abroad.These results bring hope and opportunity to LCA patients.China has more hereditary retinal disease patients,but gene therapy for hereditary retinal disease and LCA is lacking.Rightly interpreting and objectively evaluating the clinical trials of gene therapy of LCA will provide us with many important references and useful clues to further help us organize and implement clinical trials of gene therapy for hereditary retinal disease in the future.

Ophthalmic contributions of Raja Serfoji II (1798–1832).

Purpose: To investigate and describe the ophthalmic contribution of Raja Serfoji II (1798-1832). Materials and Method: A team of 2 ophthalmologists, director of laboratory services, one archeologist and a photographer visited Sarasvathi Mahal Library, March 2004. Photographs of ophthalmic records were taken and analysed. An interview of the present prince, S Babaji Rajah Bhonsle was taken. Ophthalmologic case sheets of 44 patients, 18 pictures were found. Results: Forty-four patient's ophthalmic records were found. Six records were written in Modi script, 38 were written in English and 18 drawings were found. Conclusion: In Thanjavur, King Serfoji II carried out methodical ophthalmic practices between 1798 and 1832. Both European and Indian medicines were used. Cataract Surgery was performed. Detailed ophthalmic records were maintained. The only evidence of Serfoji's amazing contribution to medicine lies in 50 charts and manuscripts.