Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10 years after onset in first eye: a case report.

BACKGROUND: Evidence-based criteria for the treatment of autoimmune retinopathy (AIR) have not been established. The pathology and clinical features of each antibody causing AIR, and its long-term course are still undetermined. We report our findings in a case of non-paraneoplastic AIR (npAIR) that developed in the fellow eye 10 years after the onset in the first eye. CASE PRESENTATION: Our patient had photophobia in both eyes and a rapidly progressing visual field defect in his right eye at the initial examination. He was diagnosed with non-paraneoplastic AIR based on the clinical findings and immunoblot analyses for anti-retinal antibodies, and he was treated with steroids. Ten years later, a visual field defect developed in the fellow eye, and a diagnosis of npAIR was made. Immunoblot analyses were positive for anti-α-enolase antibodies. He was treated with steroids, immunosuppressants, and plasma exchange. However, the response to the treatment was poor and both eyes eventually became blind. CONCLUSIONS: As best we know, this is the first case report of npAIR that developed in the fellow eye over 10 years after the development in the first eye. Long-term follow-up and a search for tumor lesions are necessary in cases of npAIR. Further understanding of the long-term course of AIR can contribute to an understanding of the pathology and treatment of npAIR.

Autosomal dominant optic atrophy with OPA1 gene mutations accompanied by auditory neuropathy and other systemic complications in a Japanese cohort.

Purpose: This study aimed to describe the genetic and clinical characteristics of four Japanese patients with autosomal dominant optic atrophy (DOA) accompanied by auditory neuropathy and other systemic complications (i.e., DOA-plus disease). Methods: Four patients from four independent families underwent comprehensive ophthalmic and auditory examinations and were diagnosed with DOA-plus disease. The disease-causing gene variants in the OPA1 gene were identified by direct sequencing. The genetic and clinical data of 48 DOA patients without systemic complications-that is, with simple DOA-were compared to those of DOA-plus patients. Results: DOA-plus patients noticed a decrease in vision before the age of 14 and hearing impairment 3 to 13 years after the development of visual symptoms. Two patients had progressive external ophthalmoplegia, and one patient had vestibular dysfunction and ataxia. The DOA-plus phenotypes accounted for 13.3% (4/30) of the families with the OPA1 gene mutations. Each DOA-plus patient harbored one of the monoallelic mutations in the OPA1 gene: c.1334G>A, p.R445H, c.1618A>C, p.T540P, and c.892A>C, p.S298R. Missense mutations accounted for 100% (4/4) of the DOA-plus families and only 11.5% (3/26) of the families with simple DOA. Conclusions: All the patients with the DOA-plus phenotype carried one of the missense mutations in the OPA1 gene. They all had typical ocular symptoms and signs of DOA in their first or second decade, and other systemic complications-such as auditory neuropathy, vestibular dysfunction, and ataxia-followed the ocular symptoms. We should consider the occurrence of extraocular complications in cases with DOA, especially when they carry the missense mutations in the OPA1 gene.

Three cases of acute-onset bilateral photophobia.

PURPOSE: To report the findings in 3 cases of bilateral negative electroretinograms (ERGs) with acute onset of photophobia. STUDY DESIGN: Retrospective case series. METHODS: The medical charts of the 3 patients were reviewed. RESULTS: A 43-year-old woman, a 68-year-old woman, and a 41-year-old woman were referred to Nagoya University Hospital. Their main symptom was bilateral acute photophobia. None of the patients had any systemic diseases or specific medical history. The decimal best-corrected visual acuity (> 0.8) and Humphrey visual fields (mean deviation > -3 dB) were relatively well preserved in all 3 patients. The optical coherence tomography (OCT) and fundus autofluorescence findings were essentially normal. Fluorescein angiography showed mild leakage in 1 patient but no abnormality in the other 2 patients. However, the ERGs of the 3 patients had the features of abnormal ERGs found in patients with incomplete congenital stationary night blindness (CSNB). Exome analyses found no pathogenic variants related to known CSNB-related genes. The symptoms and ERGs of the 3 patients have not progressed or recovered after a relatively long follow-up period. CONCLUSION: The ERG characteristics of 3 patients with bilateral photophobia were similar to those of incomplete CSNB, suggesting post-phototransductional abnormalities. The symptoms and genetic analyses indicated the possibility of an acquired condition rather than a hereditary retinal disease.

Pattern Visually Evoked Potentials in Japanese Girl With Optic Neuritis and Seropositive to Anti-myelin Oligodendrocyte Glycoprotein (MOG) Antibody.

Purpose: To describe a Japanese girl with unilateral optic neuritis who was seropositive for the anti-myelin-oligodendrocyte glycoprotein (MOG). Serial recordings of the pattern visual evoked potentials (pVEPs) were made to follow the dynamic changes of the disease activity. Observations: A 5-year-old girl developed a sudden reduction of vision and deep ocular pain in her right eye. On examination at our university hospital, the best-corrected visual acuity (BCVA) was light perception, and a swelling of the optic disc and tortuous vessels at the posterior pole of the right eye were observed. MRI demonstrated that her right optic nerve was hyperintense on short TI inversion recovery (STIR) sequence. A diagnosis of right papillitis was made, and she was treated with steroid pulse therapy followed by a gradual tapering of oral prednisolone. The visual acuity decreased to no light perception and plasmapheresis combined with high-dose intravenous immunoglobulin therapy was performed. The decimal visual acuity rapidly improved and recovered to 1.2, and no recurrence was observed for at least 1 year. On day 19, she was found to be anti-MOG antibody positive and anti-Aquaporin 4 antibody negative. pVEPs were recorded during the course of the disease process which showed the dynamic changes of the physiology of the visual pathways. The implicit times of the N75 and P100 components were prolonged in the right eye in the acute phase. The right visual acuity remained at 1.2 for at least 1 year, but the implicit times of the N75 and P100 components of the pVEPs of the right eye were still prolonged compared to left eye. Conclusion: Our findings indicate a positive relationship between the anti-MOG antibodies-positivity and the prolonged pVEPs. Further analyses of the pVEPs and other clinical findings of the optic neuritis are needed to establish the clinical significance of the anti-MOG antibodies positivity and optic neuritis for the diagnosis, treatment, and prognosis for this disease.

The Efficacy of Transcorneal Electrical Stimulation for the Treatment of Primary Open-angle Glaucoma: A Pilot Study.

The aim of this study was to evaluate the effects of transcorneal electrical stimulation in subjects with primary open-angle glaucoma. Five eyes of four male subjects with primary open-angle glaucoma (average age: 52.25 ± 14.68 years) were enrolled. The subjects underwent transcorneal electrical stimulation every 3 months according to the following procedure. A Dawson-Trick-Litzkow electrode was placed on the cornea, and biphasic electric current pulses (10 ms, 20 Hz) were delivered using a stimulator (BPG-1,BAK Electronics) and a stimulus isolation unit (BSI-2). A current that evoked a phosphene that the subject perceived in the whole visual area was delivered continuously for 30 min. Humphrey visual field testing was performed after every third transcorneal electrical stimulation treatment. Changes in mean deviation (MD) values were evaluated with a linear regression model. Transcorneal electrical stimulation was performed 18.2 ± 9.4 times over a period of 49.8 ± 23.0 months. The average pretranscorneal electrical stimulation intraocular pressure, best corrected visual acuity, and MD values were 11.8 ± 1.79 mmHg, 0.14 ± 0.19 (logMAR) and -17.28 ± 6.24 dB, respectively. No significant differences were observed in intraocular pressure before and after transcorneal electrical stimulation. However, there was a significant positive linear relationship between changes in MD values and the number of transcorneal electrical stimulation treatments (R2 = 0.176, P = 0.005, Spearman correlation R =0.294, P = 0.008). Transcorneal electrical stimulation treatment may improve glaucomatous visual field defects in subjects with primary open-angle glaucoma. Large-scale studies are necessary to confirm these preliminary findings.

Early Visual Processing is Affected by Clinical Subtype in Patients with Unilateral Spatial Neglect: A Magnetoencephalography Study.

OBJECTIVE: To determine whether visual evoked magnetic fields (VEFs) elicited by right and left hemifield stimulation differ in patients with unilateral spatial neglect (USN) that results from cerebrovascular accident. METHODS: Pattern-reversal stimulation of the right and left hemifield was performed in three patients with left USN. Magnetoencephalography (MEG) was recorded using a 160-channel system, and VEFs were quantified in the 400 ms after each stimulus. The presence or absence of VEF components at around 100 ms (P100m component) and 145 ms (N145m component) after stimulus onset was determined. The source of the VEF was determined using a single equivalent current dipole model for spherical volume conduction. All patients were evaluated using the behavioral inattention test (BIT). RESULTS: In response to right hemifield stimulation, the P100m and N145m components of the VEF were evident in all three patients. In response to left hemifield stimulation, both components were evident in Patient 3, whereas only the P100m component was evident in Patient 1 and only the N145m component was evident in Patient 2. Patient 1 exhibited impairments on the line bisection and cancelation tasks of the BIT, Patient 2 exhibited impairments on the copying, drawing and cancelation tasks of the BIT, and Patient 3 exhibited impairments on the cancelation task of the BIT. CONCLUSION: These results demonstrate that early VEFs are disrupted in patients with USN and support the concept that deficits in visual processing differ according to the clinical subtype of USN and the lesion location. This study also demonstrates the feasibility of using MEG to explore subtypes of neglect.

Improvement of visual acuity after transcorneal electrical stimulation in case of Best vitelliform macular dystrophy.

PURPOSE: To report an improvement of the visual acuity after transcorneal electrical stimulation (TES) in a case of Best vitelliform macular dystrophy (BVMD). PATIENT AND METHODS: A 26-year-old woman diagnosed with BVMD presented with reduced vision. Her best corrected visual acuity (BCVA) was reduced to 20/200 in the right eye, and TES was performed once a month for two sessions. The current of the biphasic pulses (anodic first; duration, 10 msec; frequency, 20 Hz) was delivered using a DTL-electrode, and the duration of the TES was 30 min. RESULTS: The BCVA in the right eye slowly improved after the TES, and 6 months later the BCVA was 20/25. The results of Humphrey visual field tests (VF) and multifocal ERGs (mfERGs) were only slightly changed. Two years later, the BCVA decreased, and it was improved again after another session of TES with the same parameters of the electrical pulses. CONCLUSION: The improvement of the visual acuity in our case of BVMD indicates that TES should be tried in other cases of retinal dystrophy. Further clinical and laboratory studies on TES are needed.

Clinical characteristics of occult macular dystrophy in family with mutation of RP1l1 gene.

PURPOSE: To report the clinical characteristics of occult macular dystrophy (OMD) in members of one family with a mutation of the RP1L1 gene. METHODS: Fourteen members with a p.Arg45Trp mutation in the RP1L1 gene were examined. The visual acuity, visual fields, fundus photographs, fluorescein angiograms, full-field electroretinograms, multifocal electroretinograms, and optical coherence tomographic images were examined. The clinical symptoms and signs and course of the disease were documented. RESULTS: All the members with the RP1L1 mutation except one woman had ocular symptoms and signs of OMD. The fundus was normal in all the patients during the entire follow-up period except in one patient with diabetic retinopathy. Optical coherence tomography detected the early morphologic abnormalities both in the photoreceptor inner/outer segment line and cone outer segment tip line. However, the multifocal electroretinograms were more reliable in detecting minimal macular dysfunction at an early stage of OMD. CONCLUSION: The abnormalities in the multifocal electroretinograms and optical coherence tomography observed in the OMD patients of different durations strongly support the contribution of RP1L1 mutation to the presence of this disease.

Acute Visual Field Defect following Vitrectomy Determined to Originate from Optic Nerve by Electrophysiological Tests.

PURPOSE: To present our findings on the cause of an acute visual field defect (VFD) that developed in a patient on the day after vitrectomy for proliferative diabetic retinopathy. CASE: A 50-year-old man complained of a blind area in the superior visual field that developed one day after vitrectomy. The patient had undergone uncomplicated vitrectomy for a long-duration vitreous hemorrhage associated with proliferative diabetic retinopathy. Residual vitreous hemorrhage hampered a clear view of the fundus. Goldmann perimetry showed a horizontal VFD in the superior field. The area corresponding to the VFD was examined by multifocal electroretinograms (mfERGs) and multifocal visual evoked potentials (mfVEPs). The amplitudes of the mfVEPs were reduced with prolonged implicit times especially when the superior hemifield was stimulated, while the amplitudes and implicit times were within the normal range when other parts of the visual field were stimulated. In addition, the full-field photopic ERGs and photopic negative responses were attenuated in the right eye. These findings suggested that the VFD did not originate from alterations in the retinal inner and middle layer but in the ganglion cells. The visual acuity improved to 1.2 but his optic disc became pale and the VFD remained unchanged more than 12 years after the surgery. CONCLUSION: We suggest that vitrectomy can cause ischemic optic neuropathy by interfering with the circulation associated with diabetes mellitus. Evaluations by mfERGs, mfVEPs, and full-field photopic ERGs were helpful in making the diagnosis.

Fundus autofluorescence in autosomal dominant occult macular dystrophy.

OBJECTIVE: To characterize fundus autofluorescence (FAF) images of eyes with autosomal dominant occult macular dystrophy (OMD). METHODS: All patients received a comprehensive ophthalmologic examination for diagnosis of OMD. We evaluated the FAF images in 13 eyes of 7 patients with autosomal dominant OMD by confocal scanning laser ophthalmoscopy with excitation at 488 nm and emission more than 500 nm. RESULTS: The FAF images showed unspecific weak foveal hyperfluorescence in 4 eyes of 2 patients; one showed a thin hyperfluorescence in the temporal fovea bilaterally and the other showed weak hyperfluorescence in the fovea bilaterally. The optical coherence tomographic images showed abnormalities of the photoreceptor inner segment-outer segment line and cone outer segment tip line in all patients. However, 5 patients had normal FAF images regardless of morphological abnormalities of the photoreceptor. CONCLUSIONS: Fundus autofluorescence is a useful method to acquire additional information of photoreceptor/retinal pigment epithelium function in eyes with OMD. Fundus autofluorescence will be also helpful for the differential diagnosis of eyes with OMD vs eyes with other dystrophies that have a distinctive FAF pattern.

Pattern-reversal visual-evoked potential in patients with occult macular dystrophy.

PURPOSE: Occult macular dystrophy (OMD) is a hereditary retinal disease characterized by a normal fundus, normal full-field electroretinograms (ERGs), progressive decrease of visual acuity, and abnormal focal macular ERGs. The purpose of this study was to report pattern-reversal visual-evoked potential (pVEPs) findings in OMD patients. PATIENTS AND METHOD: The pVEPs recorded from four patients with OMD (aged 42-61 years; 2 men and 2 women) were reviewed. The visual acuities ranged from 20/200 to 20/30. The amplitudes of the N-75 and P-100 (P2 amplitude) and the latency of the N-75 components (N1 latency) were analyzed. RESULTS: The mean (±SD) P2 amplitude was 2.7 ± 1.9 µV for the 5', 4.8 ± 2.9 µV for the 10', 3.2 ± 2.1 µV for the 20', and 4.4 ± 3.5 µV for the 40' checkerboard stimuli. The N1 latency was 122.2 ± 6.4 ms for the 5', 105.0 ± 11.5 ms for the 10', 97.7 ± 10.0 ms for the 20', and 91.0 ± 13.7 ms for the 40' checkerboard stimuli. The mean P2 amplitude was reduced and the N1 latency was delayed in comparison with the laboratory standard for the Keio University Hospital. CONCLUSIONS: The delayed latency and reduced amplitude suggest a major contribution of the central cone pathway to the pVEPs.

Dominant mutations in RP1L1 are responsible for occult macular dystrophy.

Occult macular dystrophy (OMD) is an inherited macular dystrophy characterized by progressive loss of macular function but normal ophthalmoscopic appearance. Typical OMD is characterized by a central cone dysfunction leading to a loss of vision despite normal ophthalmoscopic appearance, normal fluorescein angiography, and normal full-field electroretinogram (ERGs), but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly reduced at the central retina. Linkage analysis of two OMD families was performed by the SNP High Throughput Linkage analysis system (SNP HiTLink), localizing the disease locus to chromosome 8p22-p23. Among the 128 genes in the linkage region, 22 genes were expressed in the retina, and four candidate genes were selected. No mutations were found in the first three candidate genes, methionine sulfoxide reductase A (MSRA), GATA binding 4 (GATA4), and pericentriolar material 1 (PCM1). However, amino acid substitution of p.Arg45Trp in retinitis pigmentosa 1-like 1 (RP1L1) was found in three OMD families and p.Trp960Arg in a remaining OMD family. These two mutations were detected in all affected individuals but in none of the 876 controls. Immunohistochemistry of RP1L1 in the retina section of cynomolgus monkey revealed expression in the rod and cone photoreceptor, supporting a role of RP1L1 in the photoreceptors that, when disrupted by mutation, leads to OMD. Identification of RP1L1 mutations as causative for OMD has potentially broader implications for understanding the differential cone photoreceptor functions in the fovea and the peripheral retina.

Retinopathy: an overlooked adverse effect of interferon-beta treatment of multiple sclerosis.

Interferon (IFN), which is an established maintaining therapy for multiple sclerosis (MS), has been reported various adverse effects. This paper describes a case of IFN-associated retinopathy, representing an overlooked adverse effect in MS. A 46-year-old woman with diabetes mellitus was diagnosed with MS and treated with IFNbeta-1b for three years. She displayed sudden defect of the visual field and ocular fundi showed retinal cotton wool spots indicating IFN-retinopathy, which resolved rapidly after IFN was discontinued. To evaluate the prevalence of retinopathy in MS, we performed fundoscopic examination on twenty MS patients treated with IFNbeta-1b in our hospital. However, none of the patients displayed retinopathy. Only four other cases of IFN- retinopathy in MS have been reported in the literature. Therefore, IFN-retinopathy may be uncommon in MS, but neurologist should be mindful of this adverse effect and regularly check the fundus, particularly in patients with possible risk factor, diabetes mellitus.

Transcorneal electrical stimulation of retina to treat longstanding retinal artery occlusion.

PURPOSE: To report the outcome of transcorneal electrical stimulation (TES) of the visual system on long-standing retinal artery occlusion (RAO). DESIGN: Open labeled, case series. PATIENTS AND METHODS: Two patients with central RAO (15 and 33 months respectively) and one with branch RAO (26 months) underwent TES therapy. Subjective and objective ophthalmological evaluations were performed before and after the TES. The ages of the patients were 38, 49, and 63 years. The TES (20 Hz biphasic pulses, 30 minutes, up to 1100 uA) was delivered by a bipolar contact lens electrode once a month for 3 months. Perimetric and/or electrophysiological examinations were performed as outcome measures. RESULTS: The visual acuity improved by more than 0.2 logMAR units in two cases, and the visual fields were improved in all three cases. The multifocal ERGs which had been reduced in the loci corresponding to the ischemic retinal area were improved after the treatment in two cases. Neither ocular nor systemic adverse effects were observed except for transient superficial keratitis. CONCLUSIONS: TES of the retina can improve retinal function in eyes with long-standing RAOs.

Discordance between subjective perimetric visual fields and objective multifocal visual evoked potential-determined visual fields in patients with hemianopsia.

PURPOSE: To investigate the concordance between subjectively and objectively acquired visual fields in patients with subjectively determined hemianopsia. DESIGN: Retrospective observational study. METHODS: Ten patients, six men and four women, ranging in age from 28 to 68 years, were studied. Goldmann or Humphrey perimeters were used to obtain the subjectively determined visual fields for up to 25 degrees of eccentricity, and the VERIS Scientific System (Electro-Diagnostic Imaging, San Francisco, California, USA) was used to record multifocal visual evoked potential [VEPs] (mfVEPs) to obtain the objective visual fields. Each of the 60 black-and-white segments of the checkerboard stimulus was alternated according to a binary m sequence. The first slices of the second-order kernels were extracted and analyzed. RESULTS: In five cases, the visual field loci where the mfVEPs were within normal limits corresponded to the scotomatous areas obtained by conventional perimetry. In these discordant cases, the lesions (e.g., arteriovenous malformation) were located in the occipital lobe. Two of these cases had a complete recovery of the subjective visual field. The lesions of the concordant cases were located outside the occipital lobe (e.g., pituitary adenoma). In these cases, no visual field improvement was seen. The temporal crescent syndrome was ruled out in patients with posterior lesions by computed tomography (CT) or magnetic resonance imaging (MRI) findings. CONCLUSIONS: In some patients with occipital lesions, the subjective and objective visual field results are discordant, and some of them will show a recovery of the visual field deficits.

Woman with atypical unilateral Leber's hereditary optic neuropathy with visual improvement.

We describe a patient with Leber's hereditary optic neuropathy (LHON) who had a unilateral involvement and a gradual recovery of vision. A 50-year-old woman was referred to our clinic in December 2004 for the treatment of left optic neuritis. The visual acuity was 0.01 in her left eye and 1.5 in her right eye. The left eye had a central scotoma and a relative afferent pupillary defect. Ophthalmoscopy revealed a hyperaemic optic disc with indistinct margins in the left eye. Fluorescein angiography showed circumpapillary microangiopathy in both eyes and staining of the left optic disc. An nt 11778 mutation was identified and she was diagnosed with LHON. The central scotoma gradually improved, and the visual acuity had recovered to 0.3 in August 2007. LHON should still be considered even in older female patients presenting with unilateral acute visual loss when microangiopathy is seen. In such cases, molecular testing is effective in confirming a diagnosis of LHON.

Phototoxic effects of commercial photographic flash lamp on rat eyes.

BACKGROUND: To determine whether exposure of the cornea and retina of rats to flashes from a commercial photographic flash lamp is phototoxic. METHODS: Sprague-Dawley rats were exposed to 10, 100, or 1,000 flashes of the OPTICAM 16M photographic flash lamp (Fujikoeki, Japan) placed 0.1, 1, or 3 m from the eyes. Corneal damage was assessed by a fluorescein staining score, and the retinal damage by eletroretinography (ERG) and histology before and 24 h after exposure. RESULTS: Exposure of the eyes to 1,000 flashes at 0.1 m increased the fluorescein staining score significantly (P = 0.009, the Mann-Whitney test). Scanning electron microscopy (SEM) of the cornea showed a detachment of the epithelial cells from the surface after this exposure. The amplitude of the a-wave was decreased significantly by 23.0% (P = 0.026) of the amplitude before the exposure, and the b-wave by 19.7% (P = 0.0478) following 1,000 flashes at 0.1 m but not by the other exposures. TUNEL-positive cells were present in the outer nuclear layer only after the extreme exposure, but no significant decrease in retinal thickness was seen under any condition. The fluorescein staining score and ERGs recovered to control levels within 1 week. CONCLUSIONS: Light exposure to a photographic flash lamp does not induce damage to the cornea and retina except when they are exposed to 1,000 flashes at 0.1 m.

Microcirculation at optic disc rim is correlated with visual field defects in cases of anterior ischaemic optic neuropathy.

We report two cases of anterior ischaemic optic neuropathy in whom tissue blood flow at the disc rim was correlated with the visual field defect. Tissue blood flow of each eye was evaluated with Heidelberg retina flowmeter. Both cases experienced acute visual loss and an altitudinal hemianopsia associated with optic disc oedema in the affected eye. In each case, the tissue blood flow at the affected (upper or lower half) disc rim corresponding to visual field deficit was reduced compared with that at the opposite-sided half disc rim in the affected eye and with the corresponding area in the fellow eye. The reduction of blood flow in the affected half disc rim associated with the visual field defect demonstrated that retina flowmetry can detect differences in tissue blood flow between superior and inferior sectional disc rim areas as well as between eyes non-invasively.