Purpose
This study aimed to investigate the relationship between corneal decompensation following laser peripheral iridotomy (LPI) and iridocorneal endothelial contact.
Study design
Retrospective ...observational case series.
Methods
Specular microscopy images of LPI recipients with narrow angles were taken at the central cornea and the 8 midperipheral corneal regions at approximately 3 mm from the center. Eleven eyes of 11 patients had a minimum of ≤ 1600 cells/mm
2
among 8 midperipheral corneal endothelial cell densities (ECDs). Radial scans of the angles in the 8 directions were taken with ultrasound biomicroscopy (UBM) in the supine and face-down positions. The minimum and maximum angle opening distance at 750 μm from the scleral spur of the 8 directions were defined as the narrowest and widest angles, respectively. The ECD of the narrowest angle direction was compared with the ECD of the widest angle direction.
Results
When UBM was performed with the subject in the supine position, the iris and cornea at the narrowest angle were in contact in only 4 of 11 eyes, while in the face-down position, the iris and the cornea at the narrowest angle were in contact in 10 of the 11 eyes. In the face-down UBM, the midperipheral ECD of the narrowest angle direction was significantly smaller than the midperipheral ECD of the widest angle direction (
P
= 0.006).
Conclusion
The ECD of the narrow angle direction can decrease after LPI. This suggests that corneal endothelial cell damage following LPI may be due to mechanical damage from iridocorneal endothelial contact.
Purpose
To reveal the recurrence rate of Graves ophthalmopathy (GO) presenting as diplopia in the primary position for 1 year after varied doses of intravenous methylprednisolone (IVMP) followed by ...oral prednisolone, with dosing based on the magnetic resonance imaging (MRI) findings.
Study design
Retrospective study.
Methods
We analyzed the medical charts of 25 patients who were diagnosed with new-onset GO and who received treatment for diplopia in the primary position at our hospital. Treatment consisted of MRI-determined varied doses of IVMP followed by oral prednisolone. If the MRI findings showed deterioration or were unchanged after 6 g of IVMP, 3 g of IVMP was added for further treatment. Simple and multiple linear regression analyses were performed to reveal the associations between the independent variables and the dependent variable, defined as recurrence.
Results
The mean patient age (± standard deviation) was 61.3 ± 11.3 years. The female to male ratio was 15:10. Twenty-one of the 25 patients received a total of 6 g of IVMP, whilst the remaining 4 patients received a total of 9 g of IVMP. In 5 patients (20%), the GO recurred within 1 year of IVMP administration. Simple and multiple linear regression analyses showed that the MRI findings after 6 g of IVMP affected recurrence (
P
< .05).
Conclusion
This study showed that in 20% of patients, GO recurred within 1 year of administration of varied doses of IVMP, with the dosing based on the MRI findings. Furthermore, assessment of inflammation by use of MRI after 6 g of IVMP has a potential role in predicting recurrence.
Purpose
To assess the effect of maintenance therapy on visual outcomes in preventing recurrences one year after first onset in patients with aquaporin-4 antibody (AQP4Ab)-positive optic neuritis.
...Study design
Retrospective study.
Methods
The medical charts of 56 patients with optic neuritis (22 with AQP4Ab-positive and 34 with AQP4Ab-negative) at Niigata University Medical and Dental Hospital were retrospectively analyzed. Clinical characteristics, including visual acuity and number of recurrences one year after first onset, were compared among patients who were AQP4Ab-positivie with and those without maintenance therapy such as oral prednisolone and azathioprine, as well as those who were AQP4Ab-negative.
Results
The mean ages were 49.3 and 45.2 years in the AQP4Ab-positive and the AQP4Ab-negative groups. The female to male ratio was 21:1 and 18:16 in the two groups, respectively. Multiple between-group comparison showed a statistically significant difference in visual acuity one year after first onset between the AQP4Ab-positive without maintenance therapy group and the AQP4Ab-negative group (0.05 (median, same applies below) vs. 1.0, p < 0.01). There was also a statistically significant difference in the number of recurrences in the year after first onset between the AQP4Ab-positive with and without maintenance therapy groups (1 vs. 0, p < 0.01).
Conclusion
This study demonstrates that patients with AQP4Ab-positive optic neuritis without maintenance therapy had the poorest visual acuity and the most recurrences one year after first onset. These results indicate that reducing the number of recurrences with maintenance therapy could improve the visual outcomes in patients with AQP4Ab-positive optic neuritis.
To determine the course of occult macular dystrophy (OMD, Miyake's disease) and to propose stages of OMD based on the optical coherence tomographic (OCT) findings.
Sixty-one patients from 33 families ...with OMD who carried one of the proven variants of the RP1L1 gene were studied at seven centers in Japan. Ophthalmological examinations including the best-corrected visual acuity (BVCA) and OCT were performed.
The median age at the last visit was 50 years with a range of 10 to 88 years, and the median age at the symptom onset was 30 years with a range of 3 to 60 years. There were significant negative correlations between the duration of OMD and BCVA, the central retinal thickness (CRT) and the thickness between external limiting membrane and retinal pigment epithelium (ERT). The BCVA gradually decreased for 10 years after symptom onset and was stable thereafter. Kaplan-Meier survival curves of the BCVA and retinal thickness showed that all of the patients had retained a vision of 1.0 logMAR, and over 80% of the patients had retained 50% thickness of the normal CRT and ERT for at least 60 years after symptom onset. The stages of OMD based on the visual symptoms and OCT findings are proposed.
The photoreceptors do not become completely atrophic even at the late stage, which may account for the good retinal pigment epithelium (RPE) structure and normal-appearing fundus. The proposed stages facilitate the investigation of the pathogenicity of OMD and provide information to determine the effectiveness of therapeutic procedures.
Objective
Neuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin‐4 (AQP4) autoantibodies. The aim of this study was to ...elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia–neuron interaction in NMOsd.
Methods
Thirty Japanese patients with serologically verified NMOsd were assessed with a neuro‐ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP.
Results
The AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Müller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement‐dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4+ astrocytes, indicating secondary retrograde degeneration after ON.
Interpretation
Severe and widespread neuroaxonal damage and unique dynamics of astrocytes/Müller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd. Ann Neurol 2016;79:605–624
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.
Biallelic variants in the EYS gene are a major cause of autosomal recessive inherited retinal disease (IRD), with a high prevalence in the Asian population. The purpose of this study was to identify ...pathogenic EYS variants, to determine the clinical/genetic spectrum of EYS-associated retinal disease (EYS-RD), and to discover disease-associated variants with relatively high allele frequency (1%-10%) in a nationwide Japanese cohort. Sixty-six affected subjects from 61 families with biallelic or multiple pathogenic/disease-associated EYS variants were ascertained by whole-exome sequencing. Three phenotype groups were identified in EYS-RD: retinitis pigmentosa (RP; 85.94%), cone-rod dystrophy (CORD; 10.94%), and Leber congenital amaurosis (LCA; 3.12%). Twenty-six pathogenic/disease-associated EYS variants were identified, including seven novel variants. The two most prevalent variants, p.(Gly843Glu) and p.(Thr2465Ser) were found in 26 and twelve families (42.6%, 19.7%), respectively, for which the allele frequency (AF) in the Japanese population was 2.2% and 3.0%, respectively. These results expand the phenotypic and genotypic spectrum of EYS-RD, accounting for a high proportion of EYS-RD both in autosomal recessive RP (23.4%) and autosomal recessive CORD (9.9%) in the Japanese population. The presence of EYS variants with relatively high AF highlights the importance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorders.
Spasm of near reflex (SNR) involves intermittent spasm of one or more of the three near reflex components. Psychiatric disorders are one cause of SNR. We describe a patient with SNR diagnosed with ...autism spectrum disorder (ASD). A 36-year-old male with esotropia since childhood was referred due to headache and dizziness. The alternate prism cover test showed 30 prism diopters at both near and distant fixation. Four months after his first visit, he was diagnosed with ASD. Twenty-nine months after his first visit, he underwent strabismus surgery to treat concomitant esotropia. Postoperatively, the angle of strabismus improved but remained variable. Because the angle of strabismus varied, we suspected SNR; the diagnosis was performed after evaluating the patient’s microfluctuations in accommodation with Speedy-K. However, it was difficult to distinguish convergence spasm from concomitant esotropia in this patient because he has had a history of esotropia since childhood. In a patient with concomitant esotropia, if the symptoms are not exclusively due to strabismus, SNR should be suspected. Although the relationship between SNR and the pathology of ASD is unknown, it is possible that patients with ASD are more likely to develop SNR.
Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen ...patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15-77/25-94). The median visual acuity in the right/left eye was 0.52/0.40 (range, -0.08-2.00/-0.18-1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. In silico analysis of CRX variants was conducted for genotype subgroup classification based on inheritance and the presence of truncating variants. Eight pathogenic CRX variants were identified, including three novel heterozygous variants (p.R43H, p.P145Lfs*42, and p.P197Afs*22). A trend of a genotype-phenotype association was revealed between the phenotype and genotype subgroups. A considerably high proportion of CRX-RD in ADCORD was determined in the Japanese cohort (39.1%), often showing the mild phenotype (CORD) with late-onset disease (sixth decade). Frequently found heterozygous missense variants located within the homeodomain underlie this mild phenotype. This large cohort study delineates the disease spectrum of CRX-RD in the Japanese population.
To report the clinical characteristics of asymptomatic cases with RP1L1 gene mutations in four families with occult macular dystrophy (OMD).
Four asymptomatic cases from four families were selected ...from a cohort of 40 subjects (16 families) with RP1L1 pathogenic variants. Clinical data of the four asymptomatic cases and three symptomatic patients in the same families were reviewed. The three asymptomatic cases did not have any visual symptoms in either eye, and one was unilaterally affected. Ophthalmologic examinations, including spectral-domain optical coherence tomography (OCT) were performed, and the morphologic characteristics of the photoreceptor layer of the asymptomatic cases were compared to those of the symptomatic patients within the same family.
The OCT images demonstrated photoreceptor abnormalities in the parafoveal regions in all of the four asymptomatic cases (i.e., absence of the interdigitation zone and blurring of the ellipsoid zone). However, these microstructures were preserved at the foveal center. The longitudinal reflectivity profiles clearly identified this distinct pattern in the asymptomatic cases. In contrast, no distinct abnormalities were detected by other examinations including perimetry, fundus autofluorescence images, and multifocal electroretinograms (ERGs).
The sparing of the central foveal photoreceptor layer accounts for the well-preserved visual acuity in the asymptomatic patients. The sparing may represent either the initial phase of typical OMD or a subtype of macular lesion associated with OMD. It is necessary to examine asymptomatic subjects in families with OMD because some of them may progress to the typical phenotype of OMD.
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