Abnormalities of visual-evoked potentials and pupillary light reflexes in a family with autosomal dominant occult macular dystrophy

Occult macular dystrophy (OMD) is an unusual inherited or sporadic macular dystrophy characterized by an essentially normal appearing ocular fundus and normal ocular circulation determined by fluorescein angiography but with a progressive decrease of visual acuity. We present a family with OMD who have a delay in the implicit times of both the visual-evoked potentials and the pupillary light reflexes. Because these delays are usually indicative of optic nerve disorders, deciding on a diagnosis between OMD and optic nerve disorder should be done carefully. We are not aware of any studies that have reported these findings in patients with OMD.     

Progressive expansion of the hyperautofluorescent ring in cone-rod dystrophy patients

Purpose: To evaluate the expansion of the hyperautofluorescent ring and the retinal structure changes over time in cone-rod dystrophy (CRD) patients, using fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT).

Methods: Retrospective case series study. Six eyes of three CRD patients with a parafoveal hyperautofluorescent ring were studied. The diagnosis of CRD was established by the presence of the implicit time shift at 30-Hz flicker and prevalent decrease of photopic over scotopic responses on electroretinography. External and internal ring expansion was evaluated by measurements of its area at baseline and at 24-month follow-up using FAF. SD-OCT analyzed the retinal structure of the ring and the length of devoid ellipsoid zone (EZ) was measured over time.

Results: The mean age of study patients was 21 years old and the mean baseline visual acuity was 20/200. The external and internal FAF rings involving the fovea were identified in all study eyes. SD-OCT showed a normal retinal structure outside the ring. At the transitional zone of the ring, disorganization of both EZ and external limiting membrane (ELM) was observed. Inside the hyperautofluorescent ring, EZ and ELM were not identified. At 24-month follow-up examination, the mean % area increase of external and internal rings were 18.32% and 20.42%, respectively, and was concordant with the EZ band defect length enlargement.

Conclusion: Progressive expansion of hyperautofluorescent macular ring with a correspondent EZ band defect enlargement was observed over time in CRD patients.     

Electrophysiology findings in a large family with central areolar choroidal dystrophy

Purpose: To perform an electrophysiological study of central areolar choroidal dystrophy (CACD) in the affected members of a four generation family. Methods: Eight affected family members from the last three generations of a family affected by CACD were assessed by full-field electroretinograms (rod response, maximal combined response, oscillatory potentials, single-flash cone response and 30Hz flicker responses) and electro-oculograms. In addition three members of the youngest generation, who were visually asymptomatic, had pattern visual evoked potentials (PVEPs) and pattern electroretinograms (PERGs) performed. Affected status had been determined previously by genetic analysis. Results: Three youngest generation family members, who were considered affected by genetic haplotype analysis, had no visible optic nerve or retinal abnormalities. All of these subjects had abnormal PVEPs and PERGs in both eyes. Abnormalities were also detected in two of these subject's Rod ERGs, Cone ERGs and one of these subject's Maximal ERGs and 30Hz ERGs. Electrophysiological examination in the older generations demonstrated a similar, more advanced, cone and rod dysfunction. Conclusions: All affected, but clinically normal, youngest generation patients had bilaterally abnormal PVEPs and PERGs. In CACD the PVEP and PERG proved to be the most sensitive electrophysiological tests of preclincial macular dysfunction, 3/3 subjects abnormal. ERG recording to ISCEV guidelines were very useful in these cases; 7/8 subjects abnormal. The EOG was less useful; 4/8 subjects abnormal. CACD produces a widespread photoreceptor dysfunction in its later stages. This revised version was published online in July 2006 with corrections to the Cover Date.     

SPATA7: Evolving phenotype from cone-rod dystrophy to retinitis pigmentosa

Background: SPATA7 mutations have been associated with different autosomal recessive retinal degeneration phenotypes. Long-term follow-up has not been described in detail.

Materials and methods: A Hispanic patient with SPATA7 mutations was evaluated serially over a 12-year period with kinetic and static chromatic perimetry, optical coherence tomography (OCT), and fundus autofluorescence (AF) imaging. Electroretinography (ERG) was performed at the initial visit.

Results: The patient was homozygous for a mutation in SPATA7 (p.V458fs). At age 9, the ERG showed an abnormally reduced but preserved rod b-wave and no detectable cone signals. There were two islands of vision: a midperipheral island with greater cone than rod dysfunction and a central island with normal cone but no rod function. Serial measures of rod and cone vision and co-localized retinal structure showed that the midperipheral island slowly became undetectable. By age 21, only the central island and its cone function remained, but it had become more abnormal in structure and function.

Conclusion: The disease resulting from SPATA7 mutations in this patient initially presented as a cone-rod dystrophy (CRD), but changed over time into a phenotype more reminiscent of late-stage retinitis pigmentosa (RP). The differential diagnosis for both CRD and RP should include this rare molecular cause of autosomal retinal degeneration. An evolving phenotype complicates not only clinical diagnosis and patient counselling but also future strategies aimed at treating specific retinal regions.     

成年人型卵黄样黄斑营养不良的临床特征

目的研究成年人型卵黄样黄斑营养不良的临床和影像学特征。设计回顾性病例系列。研究对象北京同仁医院9例（13眼）成年人型卵黄样黄斑营养不良患者。方法分析患者的眼底表现、荧光素眼底血管造影（FFA）、相干光断层扫描（OCT）和自体荧光检查结果。主要指标FFA及OCT特征。结果所有患者均无家族史。视力在0．3及以上者8／13眼（61．5％）。所有患者均表现为黄斑区圆形卵黄样微隆起、边界清楚的、不超过1PD的视网膜下病变。FFA显示病变处呈遮蔽荧光,其旁无或显现荧光,在吸收过程中,荧光相应增加。OCT显示在视网膜色素上皮（RPE）光带前见一梭形均匀的高反射区,在吸收过程中,高反射区出现不均匀,或有小的无光反射暗区。结论黄斑区圆形卵黄样不超过1PD的视网膜下病变,无明显视网膜脱离及无病变破裂分层是本病的特点。FFA和OCT检查相结合有助于成年人型卵黄样黄斑营养不良的诊断。     

Analysis of spectral domain optical coherence tomography findings in occult macular dystrophy

Acta Ophthalmol. 2011: 89: e52–e56

Abstract.

Purpose: To describe findings of spectral domain optical coherence tomography (SD‐OCT) in the diagnosis of occult macular dystrophy (OMD). Materials and Methods: Five visually disturbed patients who had shown normal findings in full field electroretinogram (ERG), fundus photography and fluorescein angiography but abnormal findings in multifocal ERG had undergone SD‐OCT. The morphologic changes in retina and macular thickness were detected and imaged by SD‐OCT. We analysed the results of SD‐OCT including macular thickness, inner segment and outer segment (IS/OS) boundary and external limiting membrane (ELM). Results: Mean age was 41.6 (22–63) in three male and two female patients in this study. Mean central foveal thickness was 142.9 (76–161) μm. All patients had shown decreased bowing of IS/OS boundary, and five of nine eyes were noted with disrupted IS/OS boundary of the photoreceptors according to SD‐OCT. The interruption of external limiting membrane was noted in three of nine eyes. Conclusions: Spectral domain optical coherence tomography findings are useful in diagnosing OMD. Morphologic changes of the retina including deformity of the OS/IS boundary of the photoreceptors, disruption of the ELM and decreased foveal thickness may be important characteristics to consider when determining the pathophysiology and diagnosing criteria of OMD.     

Annular fundus autofluorescence abnormality in a case of macular dystrophy

Purpose: To present a case of macular dystrophy with early changes in fundus autofluorescence. Methods: A 20-year-old woman with a recent loss of visual acuity and onset of photophobia was examined. Color vision and visual field testing, fluorescein angiography, full-field and multifocal electroretinograms as well as fundus autofluorescence were performed. Results: Best-corrected visual acuity was 20/100 (right eye) and 20/60 (left eye). There was a red-green color vision defect and a relative central scotoma in both eyes. Ophthalmoscopy and fluorescein angiography were essentially normal, the presence of a dark choroid was debatable. Full-field ERG responses were normal, but the multifocal ERG showed severely reduced responses in the macular region. Both eyes showed a slight circular parafoveolar increase of fundus autofluorescence. Conclusion: Besides multifocal ERG, fundus autofluorescence aids to objectively assess the manifestation of macular dystrophies but does not discern between different types in early stages.     

Ocular phenotype of CORD5, an autosomal dominant retinal dystrophy associated with PITPNM3 p.Q626H mutation

Purpose: To describe in detail the phenotype of CORD5 in two families segregating a mutation c.1878G>C (p.Q626H) in the PITPNM3 gene. Methods: The study included 35 individuals from two different families of Swedish origin, all heterozygous for a PITPNM3 p.Q626H mutation. All participants underwent ophthalmological examination including kinetic perimetry, and in selected cases adaptometry, colour vision tests and optical coherence tomography (OCT). Electrophysiological studies were also performed. In some cases, the data were obtained from medical records. Results: The majority of patients showed subnormal visual acuity and light sensitivity from childhood. Early signs of macular degeneration were also observed. There was a progressive decrease in visual acuity leading to legal blindness in early adulthood. Electrophysiological testing showed a progressive loss of photoreceptor function restricted mainly to the cones. OCT revealed decreased macular thickness with flattened and enlarged fovea. Conclusion: Our observations of the PITPNM3 p.Q626H mutation carriers confirm that CORD5 is a disease not to mix with other retinal degenerations mapped to 17p13. The results of our clinical evaluation so far indicate that CORD5 is characterized by predominant cone dysfunction without signs of general involvement of the retinal pigment epithelium. The rod system also seems to be unaffected. In this sense, CORD5 is different from other autosomal dominant CORDs where rod involvement is present to some degree in a late phase of the disease. Some intra‐ and inter‐familial differences regarding the severity of the clinical picture were observed.     

大龄弱视患者视神经的功能和形态学评价

目的:观察大龄弱视患者视神经功能和视网膜神经纤维的变化特征。方法:选择大于12岁的大龄弱视患者30例30眼,并选取年龄相当的正常人15例30眼作为对照,利用图形视觉诱发电位(pattern visual evoked potential,P-VEP)、光学相干断层扫描(optical coherence tomography,OCT)等技术,观察大龄弱视视神经功能和神经纤维形态学的变化特征。结果:大龄弱视患者P-VEP的P100波振幅均较正常组降低、潜伏期延迟(P<0.05);OCT显示大龄弱视组视盘周围神经纤维较正常组明显降低(P<0.05)。结论:大龄弱视患者视神经传导功能和视网膜神经结构均存在异常。     

Case of cone dystrophy with normal fundus appearance associated with biallelic POC1B variants

Background: Biallelic variants of POC1B were recently reported to cause autosomal recessive non-syndromic cone dystrophy. However, the number of studies supporting this is limited, and the clinical phenotypes of cone dystrophy have not been definitively determined. The purpose of this study was to report the phenotype of a case of POC1B-associated cone dystrophy.

Materials and methods: The medical chart of one case diagnosed with cone dystrophy was reviewed.

Results: The patient was a 20-year-old Japanese man whose chief complaint was a progressive decrease in his central vision. His decimal best-corrected visual acuity was 0.2 for the right and 0.3 for the left. Fundus examinations showed no abnormalities. The photopic electroretinograms were nonrecordable, but the scotopic electroretinograms were within normal limits. Optical coherence tomography detected a blurry line in the region of the external limiting membrane and ellipsoid zone. Adaptive optics images showed sparsely distributed cone cells around the fovea. The patient was initially diagnosed with incomplete achromatopsia. Whole-exome sequence with targeted analysis identified new compound heterozygous mutations of c.G1355A (p R452Q) and c.C987A (pY329X) in the POC1B gene. The patient was then diagnosed with cone dystrophy.

Conclusions: The cone dystrophy associated with POC1B variants has features similar to achromatopsia, and genetic analyses is useful in discriminating these two diseases.     

Comparison of VEP with contrast sensitivity and other measurements of central visual function

Purpose: In order to evaluate alternative visual acuity testing techniques, especially to discriminate between small changes and for high visual acuity, we conducted a study covering several state‐of‐the‐art techniques. Methods: In this cross‐sectional study, a homogeneous cohort of healthy and young patients (n = 33; 66 eyes) underwent ETDRS vision acuity (VA) testing, testing for contrast sensitivity (CS), VA determination with spatial frequency sweep visual evoked potentials (VEP) and a series of examinations of perifoveal retinal nerve fibre layer thickness (RNFLT) using Spectralis SD‐OCT. To simulate the effect of artificial media opacity, CS, and VEP were repeated with Bangerter foils. Results: We found that Bangerter foils can be used to reduce VA effectively measured by VA testing and VEP VA. CS correlated significantly with VA (correlation coefficients ranging from 0.54 to 0.77). VEP may be used to estimate VA; nevertheless, we found no significant correlation. RNFLT did not correlate significantly with VA. Conclusion: CS seems to correlate well with VA when used for high VA. All other used examinations seem to have difficulties distinguishing between small differences in VA or when the VA is high.     

The Prevalence of Macular Cysts in Patients with Clinical Cone-Rod Dystrophy Determined by Spectral-Domain Optical Coherence Tomography

ABSTRACT

Background: To determine the prevalance of macular cysts in patients with clinical cone-rod dystrophy (CORD) using spectral-domain optical coherence tomography (SD-OCT). If macular cysts could be demonstrated in such patients, they might benefit from treatment with a carbonic anhydrase inhibitor that has been shown to be effective for treating macular cysts in various night-blinding disorders.

Material and Methods: Thirty-six CORD patients underwent a complete ophthalmic examination and an SD-OCT examination using two different systems. The presence of hypo-reflective lacunae was used to determine the presence of macular cysts.

Results: The patients’ mean age was 42.9?±?19.5 years (range 6–71 years). Mean BCVA was 1.09?±?0.64 logMAR (range no light perception to 20/25?+?2 in the better-seeing eye). All the 72 eyes studied showed a variable degree of retinal thinning, disruption of what has been referred to as the inner segment ellipsoid and outer nuclear layer (ONL) thinning of the macula. None showed evidence of macular cysts on OCT testing.

Conclusions: Although macular cysts are a common feature of various hereditary night-blinding retinal dystrophies, these were not identified in our cohort of CORD patients.     

Phenotype associated with an R120X nonsense mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa

We examined a Japanese family with X-linked retinitis pigmentosa (RP) associated with a nonsense mutation, R120X, in the RP2 gene. The 26-year-old proband presented at the age of seven years with a two-year history of night blindness. Visual disability worsened with increasing age. At age 24, visual acuity was 0.08 in both eyes. Testing for refractive error indicated mild myopia. Visual fields showed bilateral-constriction to 10 degrees. He had central macular areolar sclerosis in both eyes. Two maternal uncles had vision of light perception to hand movement in their early forties together with dense bilateral cataracts. The ocular phenotype of this family with R120X was considered severe; reported phenotypes associated with this mutation have not been uniform.     

儿童非器质性视力下降临床特征分析

目的分析儿童非器质性视力下降的临床特征,以期为临床对该疾病快速确诊、避免过度治疗提供依据。方法收集复旦大学附属眼耳鼻喉科医院神经眼科门诊诊断为非器质性视力下降的患儿(年龄<18岁)的病史及临床资料。眼科检查包括裂隙灯检查、眼底照相、最佳矫正视力(BCVA)、视野、光学相干层析成像(OCT)及图形视觉诱发电位(P-VEP)等。结果 42例确诊为非器质性视力下降的患儿中,男性13例、女性29例,男/女比为1∶2.23。平均年龄为(9.73±3.02)岁(5～17岁)。单眼患者7例,双眼患者35例。患眼BCVA集中在0.1～0.3(45.45%)及0.4～0.6(36.36%)2个程度分级。38例患者眼底检查显示视盘及黄斑形态正常,4例(7眼,9.09%)患者为假性视盘水肿。42眼视野检查异常,以管状视野、周边视野缺损、弧形缺损及不规则暗点常见,中心暗点少有。所有患者OCT视盘周围视网膜神经纤维层(RNFL)厚度及黄斑区神经节细胞-内丛状层(GCIPL)厚度均在正常范围。所有患者P-VEP P100峰时、潜伏期均未见异常。结论非器质性视力下降患儿主观检查包括BCVA、视野异常,但客观检...     

高度近视合并白内障行超声乳化吸出并人工晶状体植入手术前后P-VEP与黄斑OCT的变化

目的　观察高度近视合并白内障患者术前及术后图形视觉诱发电位（ｐａｔｔｅｒｎｖｉｓｕａｌｅｖｏｋｅｄｐｏｔｅｎｔｉａｌ,Ｐ-ＶＥＰ）、黄斑光学相干断层成像（ｏｐｔｉｃａｌｃｏｈｅｒｅｎｃｅｔｏｍｏｇｒａｐｈｙ,ＯＣＴ）的改变。方法　回顾性分析２３例（３４眼）年龄４０～７１岁行白内障超声乳化吸出联合人工晶状体植入术治疗的高度近视合并白内障患者的临床资料。于术前１ｄ及术后１个月行Ｐ-ＶＥＰ、黄斑部ＯＣＴ检查,观察低空间频率及高空间频率下Ｐ１００波的振幅、潜时和黄斑中心凹视网膜厚度。结果　术后１个月低空间频率Ｐ１００波振幅为（８．９４±４．６５）μＶ,潜时为（１０８．２５±１６．６５）ｍｓ,与术前１ｄ的振幅（５．６６±４．０２）μＶ和潜时（１１７．８５±１５．８５）ｍｓ相比差异均有统计学意义（均为Ｐ＜０．０５）。术后１个月高空间频率Ｐ１００波振幅为（７．９９±２．８２）μＶ,潜时为（１０６．０５±１６．０５）ｍｓ,与术前１ｄ的振幅（６．４１±４．０６）μＶ和潜时（１１０．４５±１９．９５）ｍｓ相比差异均有统计学意义（均为Ｐ＜０．０５）。术后１个月ＯＣＴ检查黄斑中心凹视网膜厚度为（１８８．００±７７．００）μｍ,与术前１ｄ的（１８３．００±８２．００）μｍ相比差异有统计学意义（Ｐ＜０．０５）。结论　对于高度近视合并白内障患者,Ｐ-ＶＥＰ的Ｐ１００波在白内障超声乳化吸出联合人工晶状体植入术后与术前比较,低空间频率及高空间频率的振幅升高、潜时缩短;术后黄斑中心凹视网膜厚度较术前增加。超声乳化吸出联合人工晶状体植入术治疗高度近视合并白内障是一种安全、有效的手术方法。     

Evidence supportive of a functional discrimination between photopic oscillatory potentials as revealed with cone and rod mediated retinopathies

We report on a family where four of the eleven children presented with reduced visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test, normal appearing fundi and unexpected electroretinographic findings. Light- (photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory potentials (OPs) were obtained following an accepted standard protocol. The b-wave of their photopic ERG was significantly more attenuated than the a-wave due to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within the normal range, giving to the b-wave a truncated appearance reminiscent of that seen in congenital stationary night blindness (CSNB) with myopia. Interestingly in the latter condition, which is believed to result from an ON-retinal pathway anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of normal amplitude thus resulting in an OP response pattern which complements that seen with our patients. Also of interest is the fact that, in our patients, the amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured in light-adaptation while, in normal, a non-significant 14% increase is noted; a finding which is in keeping with other studies reporting supernormal scotopic ERGs in some forms of cone dystrophies. Based on the photopic OP response pattern, our patients represent the electrophysiological complement of patients affected with CSNB. Interestingly their symptoms are also complementary, a finding which could support a functional discrimination between the photopic OPs. This revised version was published online in July 2006 with corrections to the Cover Date.     

Progressive sector retinitis pigmentosa due to c.440G>T mutation in SAG in an Australian family

ABSTRACT

Background

Heterozygous c.440 G > T mutation in the S-antigen visual arrestin (SAG) gene has been described as a cause of autosomal dominant retinitis pigmentosa (adRP) in a series of patients of Hispanic origin. This study presents the early and late clinical features and disease progression rates in an Australian family with SAG adRP.