Retinal function after scleral buckling for recent onset rhegmatogenous retinal detachment: assessment with electroretinography and optical coherence tomography

PURPOSE: To investigate central and peripheral retinal function after scleral buckling surgery for recent onset rhegmatogenous retinal detachment (RD). METHODS: Fifteen phakic patients with rhegmatogenous RD for <1 week underwent scleral buckling surgery. Clinical investigation, optical coherence tomography (OCT), full-field electroretinography (ERG), and multifocal ERG (mfERG) with fundus illumination were performed preoperatively and 6 months postoperatively. RESULTS: Anatomical success was achieved in 14 patients. mfERG amplitudes were reduced preoperatively in detached retina, with significant improvement at follow-up (P = 0.002). Foveal amplitudes improved significantly (P = 0.027). There was no significant difference in postoperative mfERG amplitudes between areas that had been preoperatively detached or attached (P = 0.739). In the subgroup of eight patients in whom the detachment engaged the fovea preoperatively, rod function improved significantly as assessed with full-field ERG (P = 0.008). In these patients, the extent of detachment ranged between 4 clock hours and 6 clock hours, as compared with 2 clock hours and 5 clock hours in the remaining patients. OCT showed subretinal foveal fluid in four patients at follow-up. CONCLUSIONS: In recent onset rhegmatogenous RD, total rod and localized central retinal dysfunction in detached retina can improve significantly after reattachment. mfERG and OCT are suitable tools for further studies of functional outcomes in RD.     

Multifocal and full-field electroretinogram changes associated with color-vision loss in mercury vapor exposure

We evaluated the color vision of mercury-contaminated patients and investigated possible retinal origins of losses using electroretinography. Participants were retired workers from a fluorescent lamp industry diagnosed with mercury contamination (n = 43) and age-matched controls (n = 21). Color discrimination was assessed with the Cambridge Colour Test (CCT). Retinal function was evaluated by using the ISCEV protocol for full-field electroretinography (full-field ERG), as well as by means of multifocal electroretinography (mfERG). Color-vision losses assessed by the CCT consisted of higher color-discrimination thresholds along the protan, deutan, and tritan axes and significantly larger discrimination ellipses in mercury-exposed patients compared to controls. Full-field ERG amplitudes from patients were smaller than those of the controls for the scotopic response b-wave, maximum response, sum of oscillatory potentials (OPs), 30-Hz flicker response, and light-adapted cone response. OP amplitudes measured in patients were smaller than those of controls for O2 and O3. Multifocal ERGs recorded from ten randomly selected patients showed smaller N1-P1 amplitudes and longer latencies throughout the 25-deg central field. Full-field ERGs showed that scotopic, photopic, peripheral, and midperipheral retinal functions were affected, and the mfERGs indicated that central retinal function was also significantly depressed. To our knowledge, this is the first demonstration of retinal involvement in visual losses caused by mercury toxicity.     

Ganzfeld and multifocal electroretinography in Malattia Leventinese and Zermatt Macular Dystrophy

BACKGROUND: To show the value of Ganzfeld electroretinography (ERG) in Malattia Leventinese (ML, or Hereditary Dominant Drusen) and Zermatt Macular Dystrophy (ZMD) and to illustrate multifocal electroretinography (mfERG) in 2 cases of ML. PATIENTS AND METHODS: In 15 patients with ML and 14 with ZMD we recorded Ganzfeld ERGs along with clinical examinations. In two patients with ML, and an we also performed a mfERG and an automated and Goldmann perimetry. All patients had a genotypic confirmation of the respective disease. For ERG measurements, the UTAS-3000 system was used, the mfERG was recorded using the RetiScan system. RESULTS: In ML, the visual acuity remained at 0.8 or higher until the 5 (th) or 6 (th) decade of life, followed by a rapid drop. In ZMD, the decrease in acuity began already in the 3 (rd) decade and followed a more continuous time course. The time course of the decrease of the ERG b-wave amplitudes was nearly identical for either disease. The mfERG showed in one case of ML a marked reduction in the macular response density but, in the second case, a normal density response pattern despite large degenerative changes at the posterior pole. In both of these patients, we found no visual field defects. CONCLUSIONS: Patient history and clinical testing raised the suspicion of a hereditary macular dystrophy. By means of Ganzfeld and multifocal electroretinography the course of the disease could be observed. However, definite diagnosis could only be established by genetic identification.     

Macular appearance by means of OCT and electrophysiology in members of two families with different mutations in RDS (the peripherin/RDS gene)

PURPOSE: To describe the phenotype using electroretinography and optical coherence tomography (OCT) in members of two families with different mutations in RDS. METHODS: DNA was extracted from blood samples and used for mutation screening by denaturing gradient gel electrophoresis (DGGE) and nucleotide sequencing of RDS exons. Patients were examined with clinical evaluation, full-field electroretinography (ERG), multifocal electroretinography (mfERG) and OCT. RESULTS: An Arg-46 --> stop codon conversion and a Ser-125 --> Leu substitution were found, respectively, in affected members of the two families. Phenotypes included retinitis pigmentosa, central areolar choroidal dystrophy, macular dystrophy and adult vitelliform maculopathy. The vitelliform lesion was clearly delineated on OCT, but mfERG showed preserved function. Optical coherence tomography showed attenuation of retinal reflectivity in two cases. CONCLUSION: By combining traditional investigations with mfERG and OCT, we were able to obtain a more refined evaluation of contributing macular and generalized retinal dysfunction, respectively, in patients with hereditary retinal disease.     

应用OCTA检测羟氯喹对系统性红斑狼疮患者黄斑区视网膜微血管形态的影响

目的　通过光学相干断层扫描血管成像（optical coherence tomography angiography,OCTA）检测羟氯喹（hydroxychloroquine,HCQ）对系统性红斑狼疮（systemic lupus erythematosus，SLE)患者黄斑区视网膜微血管形态的影响。方法　回顾性病例研究。将服用HCQ的患者60例60眼纳入研究，根据HCQ视网膜毒性的服药累积时间，将患者分为高危组（服药累积时间≥5 a）和低危组（服药累积时间<5 a），所有患者均进行光学相干断层扫描（optical coherence tomography,OCT）、OCTA、自动化视野检查（auto visual field,AVF）及多焦视网膜电图（multifocal electroretinography,mfERG）检查。结果　与低危组相比，高危组患者OCTA检查结果显示，视网膜浅表毛细血管丛和深部毛细血管丛血管密度均降低（均为P<0.05），而中心凹无血管区扩大（P<0.05）。 HCQ累积剂量和累积时间均与FAZ参数呈正相关（均为P<0.05）。在视野测试中，与低危组相比，高危组的平均偏差增加。在mfERG检查中，高危组的中心凹及旁中心凹振幅密度较低危组均有下降（均为P<0.05）。结论　OCTA通过评估视网膜微血管变化有助于检测HCQ引起的视网膜毒性。     

Localized retinal electrophysiological and fundus autofluorescence imaging abnormalities in maternal inherited diabetes and deafness

PURPOSE: To investigate retinal function in patients with maternally inherited diabetes and deafness (MIDD) and to correlate the findings with fundus autofluorescence (FAF) imaging. METHODS: FAF was imaged in five patients (age range, 49-60 years) confirmed to have the mitochondrial DNA nucleotide A3243G point mutation. Retinal function was measured by full-field (Ganzfeld) electroretinography (ERG) and pattern ERG, incorporating the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Multifocal ERG (mfERG) was also performed. For analysis of the mfERG data, five regional ring groups of equal eccentricity were formed. For each ring, the peak amplitude (defined as the difference between P1 and N1) and the implicit time of P1 were determined and compared with normative values. RESULTS: Visual acuity in the patients was between 20/20 and 20/40 (Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Irregular increased FAF signals were observed adjacent to and between areas of atrophy of the retinal pigment epithelium (RPE). Ganzfeld ERGs were within normal limits in three patients. Pattern ERG was abnormal in five eyes of three patients. mfERG peak amplitude abnormalities were particularly present in rings 2 and 3 and were consistent with the distribution of FAF abnormalities. In all but one eye, no implicit times changes were present. CONCLUSIONS: Significant mfERG abnormalities with normal Ganzfeld ERG are consistent with nonuniform damage to the central retina in MIDD, in keeping with the FAF findings. Reduced peak amplitudes with normal implicit times in the mfERG suggest localized loss of function and may indicate damage to the cone photoreceptor outer segments or cone photoreceptor loss in MIDD.     

Genotype phenotype analysis of Bietti's crystalline dystrophy in patients with CYP4V2 mutations

PURPOSE: To evaluate the genotypic and phenotypic correlations of Bietti's crystalline dystrophy (BCD) in patients with the CYP4V2 gene by mutation screening and clinical and electrophysiological assessment. METHODS: Eighteen Chinese patients in 13 families with BCD were recruited for full ophthalmic examinations, optical coherence tomography (OCT), and visual electrophysiological tests, including electrooculography (EOG), full-field electroretinography (ERG), and multifocal electroretinography (mfERG). Peripheral venous blood was obtained from all index patients and their family members for genomic DNA extraction and CYP4V2 sequence screening by direct sequencing. RESULTS: All 18 patients with BCD had mutations in the CYP4V2 gene: five were novel (Y219H, W244X, D324V, P396L, and R400C) and four had been reported. A common mutation occurred at the splice site IVS6-8del17bp/insGC of 12 patients, four being homozygous. OCT showed the presence of intraretinal crystals in all patients. Patients with more severe thinning of the retina had worse visual acuity, and there was moderate correlation between the OCT central foveal thickness and visual acuity (Spearman rho = 0.46, P = 0.005). Patients with splice site mutations (i.e., homozygous IVS6-8del17bp/insGC or compound heterozygous IVS6-8del17bp/insGC and IVS8-2A>G) had lower EOG Arden index (P = 0.014) and were more likely to have a nonrecordable scotopic full-field ERG (P = 0.003) and nonrecordable 30-Hz flicker ERG (P = 0.043). CONCLUSIONS: BCD patients with homozygous IVS6-8del17bp/insGC or compound heterozygous IVS6-8del17bp/insGC and IVS8-2A>G mutations appeared to have more severe disease phenotype based on electrophysiological testing. The level of visual loss in BCD is related to the severity of retinal thinning.     

The outer and inner retinal function in patients with multiple evanescent white dot syndrome

Background:  To investigate the outer and inner retinal function in patients with multiple evanescent white dot syndrome (MEWDS).
Methods:  The retinal function of three subjects with MEWDS was investigated using one or a combination of full-field electroretinography (ERG), multifocal electroretinography (mfERG) or recording of multifocal oscillatory potentials (mfOP).
Results:  In case 1, the scotopic, maximal, photopic and flicker ERG responses of the two eyes were similar but the amplitudes of the dark- and light-adapted OPs were markedly reduced in the affected eye. In cases 2 and 3, the ERG responses were grossly reduced in amplitude and as expected the OPs were also diminished. However, using the mfERG a residual area of 'normal' retinal function in the affected eye was identified. The local OP, assessed by the mfOP, within the residual 'normal' retinal area was reduced as compared with the corresponding retinal area of the fellow unaffected eye. Subsequently, the mfERG responses of the 'normal' retinal area were also reduced.
Conclusion:  The OPs were reduced throughout the retina in patients with MEWDS, even in the area with a normal mfERG. The electrophysiological findings suggest that functional abnormality in MEWDS may occur initially in the inner retina and subsequently involves the outer retina.     

Fundus autofluorescence and mfERG for early detection of retinal alterations in patients using chloroquine/hydroxychloroquine

PURPOSE: To evaluate and compare the value of fundus autofluorescence (FAF) imaging and multifocal electroretinography (mfERG) in early detection of retinal alterations in patients using chloroquine/hydroxychloroquine (CQ/HCQ). METHODS: FAF imaging was performed in a consecutive series of 25 patients with long-term CQ or HCQ treatment (duration, >1 year), with or without visual disturbances. In addition, mfERG was performed in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision) guidelines in 23/25 patients. RESULTS: In 10/25 patients alterations of FAF were observed. Mild changes were limited to a pericentral ring of increased FAF. More advanced stages presented as pericentral mottled loss of FAF with increased FAF in the adjacent retina and later on a complete loss of pericentral FAF. In one case, a pericentral ring was observed when ophthalmoscopy and fluorescein angiography were normal. Marked progression of FAF abnormalities was observed during a 3-year follow-up in two of three patients. With the mfERG, pericentral, central, or generalized amplitude reductions were detected in all patients with FAF abnormalities and in an additional four patients with normal FAF. CONCLUSIONS: FAF imaging can be reliably used to detect early retinal pigment epithelial alterations in CQ/HCQ retinopathy. Ophthalmoscopy and fluorescein angiography appear to be less sensitive. With the mfERG, more retinal abnormalities were detected compared with FAF imaging.     

Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of multifocal electroretinography

PURPOSE: To assess decreased retinal function associated with high cumulative doses of hydroxychloroquine using multifocal electroretinography (mfERG). DESIGN: Retrospective cross-sectional study. METHODS: Sixty-two patients referred for evaluation of hydroxychloroquine retinal toxicity. Controls were 67 normal eyes of 67 patients referred for a variety of conditions in the other eye. Visual symptoms, duration of treatment, daily hydroxychloroquine dose (milligrams and milligrams per kilogram), cumulative dose, condition for which the drug was taken, visual acuity, retinal examination, visual fields, and mfERG amplitude. The average mfERG amplitude was calculated for five concentric rings. The age-corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the other rings (e.g., R(1)/R(2), R(1)/R(3)) were compared with limits derived from control eyes. RESULTS: The incidence of characteristic mfERG abnormalities in patients referred for evaluation with cumulative hydroxychloroquine doses of more than 1250 g was nearly 50%. It was 2.8 times that found in patients with cumulative doses less than 1250 g. Significant abnormalities were seen with cumulative doses as low as 400 g. The mfERG abnormality most commonly detected was an increased R(1)/R(2) ratio. Cumulative dose was more predictive of mfERG abnormalities than daily dose (either in milligrams or milligrams per kilogram) or duration of treatment. CONCLUSIONS: Functional testing of the retina with mfERG shows locally decreased retinal function in a large fraction of patients referred for evaluation who have taken high cumulative doses of hydroxychloroquine. A prudent mfERG testing strategy is proposed.     

Biallelic Mutations in the BEST1 Gene: Additional Families with Autosomal Recessive Bestrophinopathy

Purpose: To describe the genotype and phenotype of patients with autosomal recessive bestrophinopathy (ARB), and heterozygous carriers.

Methods: The members of three unrelated ARB families were investigated. Molecular genetic analysis was performed on 11 members of these families. Ten members were examined clinically; including visual acuity, slit-lamp examination, biomicroscopy, fundus photography, and Goldmann applanation tonometry. Measurements were also made of the anterior chamber depth and axial length, and optical coherence tomography (OCT), electrooculography (EOG), and full-field electroretinography (full-field ERG) were performed. Multifocal electroretinography (mfERG) was performed on eight members of these families.

Results: Two novel combinations of missense mutations in the BEST1 gene were identified: p.R141H/p.M325T in three patients with ARB in two unrelated Norwegian families, and p.R141H/p.I201T was found in an ARB patient in a Swedish family. All four patients with ARB had clinical and electrophysiological features of ARB. All the heterozygous carriers of the p.R141H mutation were clinically normal, and showed normal OCT, EOG and full-field ERG findings, but had mildly abnormal mfERG results. Only one heterozygous carrier of the p.M325T mutation was studied and he was clinically normal, showing normal OCT and full-field ERG results, but subnormal EOG and mfERG findings. The heterozygous carrier of the p.I201T mutation was clinically normal, showing normal OCT, EOG and full-field ERG results, but subnormal mfERG results.

Conclusions: We have shown that the two novel combinations of compound heterozygous mutations p.R141H/p.M325T and p.R141H/p.I201T in the BEST1 gene can also lead to the ARB phenotype.     

Clinical phenotype in a Swedish family with a mutation in the IMPDH1 gene

PURPOSE: Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) have recently been discovered to cause a form of autosomal dominant retinitis pigmentosa (adRP). Such mutations are estimated to account for approximately 2-5% of the adRP cases among Americans of European origin and Europeans. Aiming towards an understanding of the molecular background of retinitis pigmentosa, this paper describes the phenotype of a Swedish family with a mutation in IMPDH1. METHODS: Venous blood samples were obtained from 12 family members and screened for mutations in IMPDH1. Six individuals with the mutation were examined clinically and with full-field electroretinography (ERG), dark adaptometry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). Also reviewed were the clinical findings and ERGs obtained 14 years earlier. RESULTS: The proband and eight other relatives from three generations were found to harbor the Asp226Asn mutation in IMPDH1. These individuals, from three generations, showed clinical and electrophysiological signs of retinitis pigmentosa. The cone responses to the full-field, 30-Hz flicker ERG demonstrated an unusual pattern, with implicit times within normal limits or only slightly prolonged. Rod ERG responses, however, were undetectable. OCT showed intraretinal fluid and swelling, changes that were more pronounced in younger individuals. mfERG showed residual preserved central function. The older the individual, the smaller the area of preserved central function. CONCLUSION: In this family with a mutation in IMPDH1, we found a specific phenotype with rod function affected more than cone function, foveal edema, and central retinal function preserved for a long period of time. Foveal edema could be a pathogenic feature in this form of retinal degeneration.     

Retinal dysfunction in patients treated with vigabatrin

PURPOSE: To present the current knowledge of vigabatrin influence on the retinal function and to introduce a case report of toxic retinopathy diagnosed in our laboratory, in patient treated with vigabatrin. MATERIAL AND METHODS: A review study based on other authors', concerning the role of diagnostic tests like: perimetry, flash electroretinography (ERG), multifocal electroretinography (mfERG), electrooculography (EOG) in patients treated with vigabatrin and presentation of toxic retinopathy in drug-resistant epileptic patient treated with vigabatrin. RESULTS: In vigabatrin treated patients a functional or structural retinal changes may occur, what can be measured by electrophysiological and visual field testing. Irreversible abnormalities of visual field and ERG tests results prove the toxic character of retinopathy in presented vigabatrin treated patient. CONLUSIONS: ERG tests and visual field assessment should be performed in patients treated with vigabatrin. Initial abnormalities occurrence should be a signal for considering the change of therapy.     

Full-field ERG, multifocal ERG and multifocal VEP in patients with retinitis pigmentosa and residual central visual fields

PURPOSE: To evaluate (with three different electrophysiological methods) the residual retinal function in a selected group of patients with retinitis pigmentosa and remaining small central visual fields. METHODS: Fourteen patients from several different genetic subgroups, who had been followed with visual acuity and visual field testing for periods up to 32 years, were examined. Ophthalmological examination included full-field electroretinography (ERG), multifocal electroretinography (mfERG) and multifocal visual evoked potential (mfVEP). RESULTS: The ERGs were severely reduced in all patients. The mfERGs demonstrated the residual central retinal function in five of the patients. The mfVEPs showed measurable amplitudes centrally in most of the patients. The follow-up examinations demonstrated the slowly progressive course of the disease with preservation or only slight further loss of visual fields over a period of 7-32 years. CONCLUSION: Patients with retinitis pigmentosa may not always follow the typical natural course with progressive loss of visual fields, which may in some patients remain unaffected over several decades. Multifocal ERG and mfVEP may be clinically useful for evaluating remaining visual function in these patients.     

Variant phenotype of Best vitelliform macular dystrophy associated with compound heterozygous mutations in VMD2

PURPOSE: To characterize the phenotype of members of a Swedish family with Best macular dystrophy and two distinct mutations in VMD2. METHODS: Venous blood samples were obtained from six family members and screened for mutations in VMD2. Six individuals were examined clinically, four of whom were further investigated with full-field electroretinography (ERG), electro-oculography (EOG), multifocal electroretinography (mfERG), and optical coherence tomography (OCT). RESULTS: The VMD2 mutations resulting in Arg141His and Tyr29stop were identified in family members. Two individuals harbored both mutations, one mutation in each VMD2 allele. These two family members had an abnormal EOG and their full-field ERG demonstrated widespread degeneration with a prolonged implicit time in the cone 30-Hz flicker ERG. MfERG verified reduction of the central retinal function and OCT demonstrated intraretinal fluid, swelling, and thickening of the outer retina-RPE-choroid complex (ORCC). CONCLUSION: A previously undescribed severe form of Best macular dystrophy is associated with compound heterozygous mutations in VMD2.     

Multifocal electroretinographic changes in patients receiving hydroxychloroquine therapy

PURPOSE: To evaluate the longitudinal changes in multifocal electroretinography (mfERG) in patients receiving hydroxychloroquine and to assess the effects of cumulative hydroxychloroquine dose on mfERG. DESIGN: Prospective cohort study. METHODS: Twenty-four eyes in 12 patients receiving hydroxychloroquine underwent mfERG recordings at baseline and 1 to 2 years later. The first negative (N1) and first positive (P1) response amplitudes and peak latencies were compared with normal controls. Serial changes in the pattern of mfERG abnormalities and in response amplitudes and peak latencies were also compared between eyes in which hydroxychloroquine therapy was continued or stopped. Correlation analyses were performed to assess the effects of a cumulative dose of hydroxychloroquine on mfERG. RESULTS: At baseline, reductions in N1 and P1 response amplitudes were observed in patients receiving hydroxychloroquine compared with controls. At follow-up, in addition to the reductions in N1 and P1 response amplitudes, increases in P1 peak latencies compared with controls were observed. In patients who stopped hydroxychloroquine therapy, there were significant increases in N1 and P1 response amplitudes at follow-up mfERG. CONCLUSIONS: Patients receiving hydroxychloroquine showed a longitudinal decline in retinal function; patients who stopped hydroxychloroquine therapy showed improvement. Although these data are insufficient to demonstrate the sensitivity of mfERG for evaluating early hydroxychloroquine toxicity, the results suggest that serial mfERG assessment may help detect early retinal changes associated with hydroxychloroquine therapy. Further studies with long-term results will be useful in clarifying the value of mfERG in evaluating early retinal toxicity due to hydroxychloroquine.     

Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update

Purpose To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies. Methods Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod dystrophy (GUCA1A, RPGR, RIMS1), “cone dystrophy with supernormal rod ERG” (KCNV2) and X-linked retinoschisis (RS1). International-standard full-field and pattern electroretinography (ERG; PERG) were performed. Some patients with rod-cone or cone-rod dystrophy underwent multifocal ERG (mfERG) testing and photopic and scotopic fine matrix mapping (FMM). Results In patients with RP, the radius of the parafoveal ring of high density correlated with PERG P50 (R = 0.83, P < 0.0005, N = 62) and encircled areas of preserved photopic function. In the other patients, AF rings either resembled those seen in RP or encircled an area of central atrophy. Ring radius was inversely related to the PERG P50 component in 4 of 18 cases with a detectable response. FMM showed that arcs of high density were associated with a gradient of sensitivity change. Conclusions Parafoveal rings of high density autofluorescence are a non-specific manifestation of retinal dysfunction that can occur in different retinal dystrophies. Electrophysiology remains essential for accurate diagnosis. The high correlation of autofluorescence with PERG, mfERG and FMM demonstrates that AF abnormalities have functional significance and may help identify suitable patients and retinal areas amenable to future therapeutic intervention.     

Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy

The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7±3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P=0.001 and P=0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the dark-adapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function.     

Clinical Phenotype in a Swedish Family with a Mutation in the IMPDH1 Gene

Purpose: Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) have recently been discovered to cause a form of autosomal dominant retinitis pigmentosa (adRP). Such mutations are estimated to account for approximately 2–5% of the adRP cases among Americans of European origin and Europeans. Aiming towards an understanding of the molecular background of retinitis pigmentosa, this paper describes the phenotype of a Swedish family with a mutation in IMPDH1. Methods: Venous blood samples were obtained from 12 family members and screened for mutations in IMPDH1. Six individuals with the mutation were examined clinically and with full-field electroretinography (ERG), dark adaptometry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). Also reviewed were the clinical findings and ERGs obtained 14 years earlier. Results: The proband and eight other relatives from three generations were found to harbor the Asp226Asn mutation in IMPDH1. These individuals, from three generations, showed clinical and electrophysiological signs of retinitis pigmentosa. The cone responses to the full-field, 30-Hz flicker ERG demonstrated an unusual pattern, with implicit times within normal limits or only slightly prolonged. Rod ERG responses, however, were undetectable. OCT showed intraretinal fluid and swelling, changes that were more pronounced in younger individuals. mfERG showed residual preserved central function. The older the individual, the smaller the area of preserved central function. Conclusion: In this family with a mutation in IMPDH1, we found a specific phenotype with rod function affected more than cone function, foveal edema, and central retinal function preserved for a long period of time. Foveal edema could be a pathogenic feature in this form of retinal degeneration.     

成人型神经元核内包涵体病相关视网膜病变的多模式影像学分析

目的分析成人型神经元核内包涵体病(NIID)患者的眼部临床表现及其特征。方法对5例经皮肤活检及NOTCH2NLC基因检测GGC重复扩展突变确诊的成人型NIID患者进行详尽眼科检查,包括最佳矫正视力(BCVA)、眼底照相、自发荧光、中心视野、光学相干层析成像(OCT)、视网膜电图(ERG)、多焦ERG(mfERG)以及超声生物显微镜(UBM)等,收集特征性改变。结果5例均发现视网膜结构与功能改变,病变主要位于视盘旁及后极部,OCT表现为不同程度的椭圆体带缺失及黄斑区节细胞层弥漫性变薄,ERG和mfERG表现为相应部位不同程度的反应降低,瞳孔缩小的患者可伴有睫状突肥大和浅前房。结论NIID患者具有视网膜变性特征,以外节感光细胞层和内节神经节细胞受累为主,瞳孔受累的患者可存在潜在闭角型青光眼风险。