Mutation c. 1142 del G in the <Emphasis Type="Italic">PRPF31</Emphasis> Gene in a Family with Autosomal Dominant Retinitis Pigmentosa (RP11) and Its Implications

Purpose

To identify a mutation in the PRPF31 gene in a family (Family K) with autosomal dominant retinitis pigmentosa (adRP) linked to 19q13.4 (RP11) and to find the frequency of mutations in the PRPF31 gene among Japanese families with adRP.

Methods

Genomic DNA specimens were prepared from five symptomatic and two asymptomatic members of Family K and an additional 39 patients of 39 unrelated families with adRP. Coding regions of the PRPF31 gene were amplified by polymerase chain reaction. The amplicons were analyzed by a direct sequencing method.

Results

All seven family members had a heterozygous c.1142delG mutation in the PRPF31 gene, which was identical to the mutation previously reported in a different Japanese family. No other mutation was found in the PRPF31 gene among the 39 additional patients with adRP.

Conclusion

Although the frequency of mutations in the PRPF31 gene is about 2.5% in Japanese families with adRP, it is possible that c.1142delG is a common mutation among Japanese patients with adRP associated with mutations in the PRPF31 gene.?Jpn J Ophthalmol 2007;51:45–48 © Japanese Ophthalmological Society 2007

     

A novel mutation in the <Emphasis Type="Italic">PRPF31</Emphasis> in a North Indian adRP family with incomplete penetrance

Purpose

To identify the underlying genetic defect for non-syndromic autosomal dominant retinitis pigmentosa (adRP) with incomplete penetrance in a North Indian family.

Methods

Family history and clinical data were collected. Linkage analysis using 72 fluorescently labeled microsatellite markers flanking all the 26 candidate genes known for adRP was performed. Mutation screening in candidate gene at the mapped region was performed by bi-directional DNA sequencing.

Results

Positive two-point lod scores?>?1.0 (θ?=?0.000) suggestive of linkage were obtained with markers D19S572, D19S927 and D19S926 at 19q13.42, in the vicinity of PRPF31 gene. Mutation screening in all the 14 exonic regions and intron–exon boundaries of PRPF31 revealed a novel change, i.e. c.896G>A (p.Cys299Tyr) in exon eight. The observed change segregated in heterozygous form in all the six affected members and in three carriers, consistent with incomplete penetrance. This substitution was not observed in tested 15 unaffected members and in 200 ethnically matched controls.

Conclusion

Present study describes mapping of a locus for non-syndromic adRP with incomplete penetrance at 19q13.42 in a North Indian family and identifies a novel missense mutation (p.Cys299Tyr) in PRPF31 localized at the mapped interval. The observed substitution lies in the NOP domain of PRPF31 that exhibit RNA and protein binding surfaces and thus may interfere in the formation of spliceosome complex. Due to p.Cys299Tyr substitution hydrogen bonds are generated, which may result in conformational changes and PRPF31 protein deformity. Present findings further substantiate the role of PRPF31 in adRP with incomplete penetrance and expand the mutation spectrum of PRPF31.

     

Heterozygous deletion of the <Emphasis Type="Italic">OPA1</Emphasis> gene in patients with dominant optic atrophy

Purpose

Several OPA1 variants cause dominant optic atrophy (DOA), the most common hereditary optic atrophy. Here, we describe a newly discovered OPA1 deletion in 3 patients with DOA.

Methods

A female proband, her brother, and her mother underwent complete ophthalmologic examinations that included optical coherence tomography and visual field assessments using a Humphrey Field Analyzer with both standard automated perimetry (SAP) and short-wavelength automated perimetry (SWAP). Genomic DNA from each patient was examined to detect genomic rearrangements involving OPA1; the genetic analysis involved both multiplex ligation probe amplification and conventional Sanger sequencing.

Results

Each patient had temporal optic disc pallor and significant thinning of the retinal nerve fiber layer in both eyes, although there was phenotypic variability among the patients that ranged from asymptomatic to moderately decreased visual acuity. For the affected brother and mother, the mean deviation values from SAP were within the normal range, whereas those from SWAP were significantly below the normal range (P < .05). The genetic analysis identified a newly discovered heterozygous deletion that encompasses exons 9–14 and revealed a breakpoint junction that directly connects intron 8 to intron 14.

Conclusions

This newly described deletion is likely to lead to loss of function in the functionally important GTPase domain encoded by exons 9–16, and the heterozygosity suggested that haploinsufficiency caused the phenotypes. The deletion may be associated with mild DOA phenotypes ranging from asymptomatic to moderately decreased visual acuity.

     

Binocular visual function of myopic pseudophakic monovision

Purpose

To compare binocular visual function of myopic pseudophakic patients with myopic monovision to patients without monovision.

Study design

Randomized comparative study

Methods

Sixty patients were randomized to one of two groups: patients whose refraction was targeted to -2.75 diopters (D) in the dominant eye and -1.75D in the nondominant eye (myopic monovision group), and patients whose refraction was targeted to -2.75D bilaterally (non-monovision group). Binocular uncorrected and corrected visual acuity at various distances was measured using an all-distance vision tester, and contrast visual acuity and near stereoacuity were examined.

Results

In the myopic monovision group mean refraction was -2.74D in the dominant eyes and -1.94D in the nondominant eyes, and in the non-monovision group it was -2.96D bilaterally. Mean binocular uncorrected distance (UDVA) and intermediate visual acuity (UIVA) from 0.5 m to 5.0 m were significantly better in the myopic monovision group than in the non-monovision group (P≤ 0.0134), while binocular uncorrected near visual acuity (UNVA) at 0.3 m did not differ significantly between groups. The distribution of UIVA and UDVA was significantly better in the myopic monovision group (P≤ 0.0035). Corrected visual acuity at any distance, photopic and mesopic contrast visual acuity, and stereoacuity did not differ significantly between groups.

Conclusion

Patients with myopic monovision exhibited significantly better binocular UIVA and UDVA than those without monovision, while UNVA, corrected visual acuity, contrast sensitivity, and stereoacuity were comparable between groups, suggesting that this method is useful for patients who want to see near and intermediate distances without spectacles.

     

Comparing distance visual acuity measurement with a novel eye chart and the Landolt C chart in a population of children aged 6–18 years

Purpose

The Handy Eye Chart? is designed to assist in evaluating the visual acuity of patients with non-standard communication styles. The Handy Eye Chart? has been previously validated against the early treatment diabetic retinopathy study (ETDRS) chart. The aim of this research is to compare visual acuity outcomes with The Handy Eye Chart? against the international gold standard, the Landolt C chart, in a population of children.

Methods

Sixty participants between the ages of 6 and 18 were recruited at the Pediatric Section of the Department of Ophthalmology at the Emory Eye Center. Visual acuity was evaluated using The Handy Eye Chart? and the Landolt C Chart, altering the order of administration between charts. The visual acuity data were compared using t test, linear regression, and Bland–Altman analysis.

Results

The mean difference in visual acuity was 0.02 logMAR (CI 0.009–0.04, p = 0.002). The correlation coefficient was 0.98. The Bland–Altman analysis shows the 95% limits of agreement between the charts to be ?0.14 to 0.09 logMAR.

Conclusions

The Handy Eye Chart? is a valid measure of visual acuity when compared with the international gold standard, the Landolt C Chart.

     

Genetic diversity and persistent colonization of <Emphasis Type="Italic">Enterococcus faecalis</Emphasis> on ocular surfaces

Purpose

Enterococcus faecalis causes severe acute endophthalmitis and often leads to poor visual outcomes. Conjunctival bacterial cultures occasionally grow atypical bacteria including E. faecalis, which can potentially contribute to the development of postoperative endophthalmitis. However, the characteristics of these ocular E. faecalis strains are unknown. This study is the first attempt to determine the population characteristics of E. faecalis clinical isolates from eye infections and ocular commensals.

Study design

Retrospective

Methods

Twenty-eight E. faecalis ocular isolates were collected from 23 patients at 3 referring hospitals. The multilocus sequence typing (MLST) data were analyzed using the eBURST program. Phenotypes of cytolysin and gelatinase, antibiotic susceptibility, and mutations of the quinolone resistance-determining regions (QRDRs) of gyrA and parC were also examined. Pulsed-field gel electrophoresis (PFGE) was performed for strains from the same patients.

Results

PFGE revealed that 3 patients retained identical strains for 10 months to 2 and a half years. MLST identified 12 sequence types (STs), which were clustered into 3 clonal complexes (CCs) and 8 singletons, with ST179 the largest. Thirteen of the 23 isolates (56.5%) belonged to CC58, CC8, or CC2, which have previously been reported to be major CCs. Six of the 23 strains (26.0%) exhibited high-level quinolone resistance derived from mutations of the QRDRs in both gyrA and parC.

Conclusions

The sequence types of E. faecalis ocular isolates were divergent, with no eye-specific lineages observed. Persistent colonization of E. faecalis on the ocular surface was demonstrated in patients with chronic ocular surface diseases.

     

Short-term effect of additional apheresis on visual acuity changes in patients with steroid-resistant optic neuritis in neuromyelitis optica spectrum disorders

Purpose

To evaluate temporal changes in visual acuity in patients with steroid-resistant optic neuritis (ON) in neuromyelitis optica spectrum disorders (NMOSD) after apheresis.

Design

Retrospective observational study, clinical case series

Subjects and methods

We reviewed the medical charts of 15 eyes of 9 consecutive patients with ON in NMOSD who underwent apheresis between March 2010 and September 2017. All patients were seropositive for anti-aquaporin 4 (AQP4) antibody and resistant to steroid pulse therapy. Apheresis was performed by either simple plasma exchange or/and immune adsorption therapy.

Results

Twelve eyes (80%) showed improvement with logMAR?>?0.3 at 1 month after apheresis. Within 1 month after apheresis therapy, logMAR on average significantly decreased, the magnitude of change being greatest within the first week. Thereafter visual acuity became stable in 10 of the 11 eyes, until 12 months. However, two eyes (12%) showed recurrence of visual acuity reduction 3 months after the cessation of apheresis. There were a few serious complications during and after apheresis, but these were completely treatable.

Conclusions

Additional apheresis therapy rapidly improves the visual acuity of steroid-resistant seropositive AQP4 ON.

     

Comparison of visual outcomes and reading performance after bilateral implantation of multifocal intraocular lenses with bilateral monofocal intraocular lenses

Purpose

To compare the visual acuity outcomes, contrast sensitivity function (CS) and reading ability in patients with bilateral multifocal intraocular lenses and patients with bilateral monofocal lenses.

Setting

Vizyon Eye Center, Denizli, Turkey.

Design

Comparative case series.

Methods

Consecutive bilateral cataract patients having implantation of Acriva Reviol MFM 611 multifocal IOLs (Group A) or Acriva BB UD 613 monofocal IOLs (Group B) were included. Parameters analyzed 6 months postoperatively included monocular uncorrected distance (UDVA), binocular uncorrected intermediate (UIVA), binocular uncorrected near (UNVA), CS and bilateral reading performance using MN Read.

Results

The study evaluated 42 eyes in Group A and 40 eyes in Group B. There were no statistically significant differences in UDVA between two groups postoperatively (p = .39). Binocular UIVA and binocular UNVA are better in Group A (p = .00, p = .00). Under photopic and scotopic conditions, contrast sensitivity results were decreased in Group A, especially at high spatial frequencies. No statistically difference were found in reading acuity, critical print size and maximum reading speed between two groups (p = .57, p = .62, p = .22).

Conclusions

This study concludes that multifocal lenses are reliable and efficient replacements for reading glasses since they significantly improve the vision for near or intermediate distance activities.

     

Fixation preference test: reliability for the detection of amblyopia in patients with strabismus and interexaminer agreement

Purpose

The purpose of this study was to analyze the reliability of the fixation preference test (FPT) in the detection of amblyopia, and to determine interexaminer agreement.

Methods

Eighty patients whose visual acuity could be tested objectively and had a horizontal misalignment of more than 10 prism diopters were enrolled. The best corrected visual acuity (BCVA) and orthoptic findings were all recorded. Non-preferred eye in primary position and fixation preference grade were assessed independently by two masked experienced examiners. The primary outcome measures were reliability of FPT in terms of its correlation with BCVA and interexaminer agreement.

Results

There was no significant correlation between fixation preference grades and interocular visual acuity difference as well as the type and amount of deviation, the presence of fusion, stereopsis, anisometropia, and previous strabismus surgery for none of the examiners (p > 0.05 for all). Sensitivity was 52.0% for examiner 1 and 54.0% for examiner 2 while specificity was 50.0 and 46.7%, respectively. Interexaminer agreement was 76.7% (p < 0.001) for all patients.

Conclusions

FPT is widely used in children particularly when the visual acuity cannot be determined in an objective manner. The test may not be accurate and reliable in the detection of amblyopia and also in predicting the visual acuity difference between both eyes, even though it was found to show a high degree of agreement between examiners. In conclusion, it should be kept in mind that the reliability of FPT may be limited and the results should be interpreted with caution and be supported by other tests.

     

<Emphasis Type="Italic">MTHFR</Emphasis> and <Emphasis Type="Italic">MTHFD1</Emphasis> gene polymorphisms are not associated with pseudoexfoliation syndrome in South Indian population

Purpose

Pseudoexfoliation syndrome (PEX) is a late onset disorder of extracellular matrix turnover, associated systemically with cardiovascular and cerebrovascular disease. To evaluate the suggested association of polymorphisms of homocysteine metabolism genes MTHFR (rs1801131, rs1801133) and MTHFD1 (rs8006686) with PEX.

Methods

A case–control association study was undertaken, comprising a total of 1472 individuals including 860 unrelated PEX cases and 612 ethnic-matched cataract controls (CC). All the study subjects were genotyped for three SNPs using the TaqMan allelic discrimination assay. Association and statistical analysis were performed with PLINK 1.07 and STATA 11.1.

Results

Among the three SNPs genotyped, MTHFR polymorphisms did not exhibit significant association with PEX (rs1801131; p = 0.549, rs1801133; p = 0.408). The intronic SNP rs8006686 showed nearly significant association (p = 0.069), and however did not remain significant after Bonferroni correction.

Conclusion

Our study suggests no significant genetic association of MTHFR (rs1801131, rs1801133) and MTHFD1 (rs8006686) polymorphisms in South Indian PEX patients.

     

Ocular acne rosacea in tertiary eye center in Saudi Arabia

Purpose

To report the most common presenting signs and symptoms of ocular rosacea for timely diagnosis and management.

Methods

A retrospective chart review of 23 patients with a diagnosis of acne rosacea or a non-specific diagnosis was performed at a tertiary eye hospital. Patients with lid changes such as recurrent blepharitis; meibomianitis; recurrent chalazia; facial skin change such as papules, telangiectatic blood vessels, and/or rhinophyma were included. Data were collected on patient demographics, presenting symptoms, visual acuity, dermatologic findings and treatment.

Results

There were 23 patients documented with acne rosacea with dermatologic facial findings associated with lid and/or corneal findings of peripheral thinning and vascularization. Two cases had a serious spontaneous peripheral corneal perforation. Most of the patients had no clinically significant change in visual acuity.

Conclusion

The diagnosis of ocular acne rosacea was straightforward despite non-specific findings. Diagnostic delay can result in serious complications.

     

Treatment of Branch Retinal Vein Occlusion induced Macular Edema with Bevacizumab

Background

Branch retinal vein occlusion is a frequent cause of visual loss with currently insufficient treatment options. We evaluate the effect of Bevacizumab (Avastin^®) treatment in patients with macular edema induced by branch retinal vein occlusion.

Methods

Retrospective analysis of 32 eyes in 32 patients with fluorescein angiography proven branch retinal vein occlusion, macular edema and Bevacizumab treatment. Outcome measures were best corrected visual acuity in logMAR and central retinal thickness in OCT.

Results

Visual acuity was significantly better 4 to 6 weeks after Bevacizumab treatment compared to visual acuity prior to treatment (before 0.7 ± 0.3 and after 0.5 ± 0.3; mean ± standard deviation; p < 0.01, paired t-test). Gain in visual acuity was accompanied by a significant decrease in retinal thickness (454 ± 117 to 305 ± 129 μm, p < 0.01, paired t-test). Follow up (170, 27 – 418 days; median, range) shows that improvement for both visual acuity and retinal thickness last for several months after Bevacizumab use.

Conclusion

We present evidence that intravitreal Bevacizumab is an effective and lasting treatment for macular edema after branch retinal vein occlusion.

     

Okuläre elektrische Stimulation

Background

Electrical stimulation has a long history in ophthalmology. Subthreshold electrical stimulation can have beneficial therapeutic effects on hereditary degenerative retinal diseases. Suprathreshold stimulation is able to elicit visual perceptions and, if multielectrode fields are arranged as an array, usable pictures can be perceived by blind patients.

Objectives

This is a review article on the current situation and studies on therapeutic transcorneal electrical stimulation. Moreover, the challenges, surgical concepts and visual results of active retinal implants are discussed.

Material and methods

This article gives an overview on transcorneal electrical stimulation and active retinal implants based on published results, with special emphasis on the clinical application.

Results

The results of initial controlled studies on therapeutic transcorneal electrical stimulation in hereditary retinal diseases were very promising. The largest controlled study so far in patients with retinitis pigmentosa (RP) has yielded many positive trends and some significant improvements in electrophysiological data. Currently, two retinal implants have regulatory approval, the Argus II retinal prosthesis system® (SecondSight®) and the Alpha-IMS© (Retina Implant AG). Both systems can be used to improve visual perception and under test conditions can achieve visual acuities of 0.02 and 0.04, respectively.

Conclusion

In-depth analyses and follow-up studies in larger patient groups are currently planned to definitively clarify the potential of therapeutic transcorneal electrical stimulation in RP patients. The challenges of currently available active retinal implants are the technical biostability and the limited spatial resolution.

     

Concentration of acute phase factors in vitreous fluid in diabetic macular edema

Purpose

Diabetic retinal maculopathy is associated with acute and chronic local inflammation. We measured the concentrations of acute phase factors in vitreous fluid of patients with diabetic macular edema (DME) and examined their relations to visual acuity and central retinal thickness (CRT) both before and after vitrectomy.

Study design

Retrospective.

Methods

Vitreous fluid was collected during vitreoretinal surgery from 19 patients with DME and 12 control subjects with epiretinal membrane. The concentrations of acute phase factors (α2-macroglobulin, haptoglobin, C-reactive protein, serum amyloid P and A, procalcitonin, ferritin, tissue plasminogen activator, fibrinogen) and vascular endothelial growth factor (VEGF) were measured with multiplex assays. CRT of macular edema was measured by optical coherence tomography (OCT).

Results

The levels of serum amyloid P, procalcitonin, ferritin, and fibrinogen in vitreous fluid were increased in DME patients compared with control subjects. The levels of procalcitonin and fibrinogen in DME patients were inversely correlated with visual acuity both before and 3 months after vitrectomy but not 6 months postsurgery. The concentrations of these four factors were not correlated with either CRT or the vitreous levels of VEGF in DME patients.

Conclusion

Acute phase factors may contribute to local inflammation in DME and may therefore influence disease progression.

     

Topical non-steroidal anti-inflammatory drugs for the treatment of cystoid macular edema post Descemet’s stripping automated endothelial keratoplasty

Purpose

To investigate the effectiveness of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of cystoid macular edema (CME) post Descemet’s stripping automated endothelial keratoplasty (DSAEK).

Study design

Retrospective observational study

Methods

In this study of 334 patients who underwent DSAEK at the Baptist Eye Institute, Kyoto, Japan between July 2011 and December 2015, 18 patients with postoperative CME (determined by optical coherence tomography) treated with topical NSAIDs after the onset of CME were included.

Results

At CME onset, 17 of the 18 patients were treated with bromfenac eye drops and 1 was treated with nepafenac eye drops. Post initiation of treatment with topical NSAIDs, CME in 17 (94.4%) of the 18 patients improved at 1 month and all cases completely recovered within 3 months. At 12-months post initiation of treatment, 61.1% (n?=?11) of patients achieved a visual acuity (VA) of 20/40 or better, and there was no significant difference of VA between the patients with or without an episode of postoperative CME (P?=?0.55).

Conclusion

The administration of topical NSAID eye drops was found to be effective in treating patients with CME post DSAEK.

     

Long-term results of cataract surgery in patients with anterior uveitis

Purpose

This study was aimed to assess the long-term results of phacoemulsification and posterior chamber intraocular lens implantation in patients with anterior uveitis.

Methods

Patients with complicated cataract secondary to anterior uveitis who underwent phacoemulsification and posterior chamber intraocular lens implantation were included in this study. Long-term results and all complications were evaluated throughout the postoperative 4 years.

Results

A total of 55 eyes of 48 patients were identified in this study. Cases with anterior uveitis were categorised into four aetiologic groups. Of the 55 eyes, 22 (19 patients) had idiopathic anterior uveitis, 10 (9 patients) had viral anterior uveitis, 10 (9 patients) had Fuchs’ anterior uveitis and 13 (11 patients) had anterior uveitis associated with collagen vascular diseases. Preoperative macular oedema was more frequent (63.6%) in the idiopathic group than in the other groups (p < 0.001). The success rates of the best corrected visual acuity of 20/40 or better ranged from 80.0 to 100.0% in the groups. While postoperative increased intraocular pressure rate was statistically significantly higher in the Fuchs’ group (p = 0.047), there was no statistically significant difference in other complication rates between the groups.

Conclusions

The long-term outcomes of phacoemulsification with intraocular lens implantation in patients with uveitic cataract were satisfactory with excellent visual acuity and relatively low complication rates.

     

The effectiveness of disc synoptoscope on patients with abnormal binocular vision: a prospective cohort study

Purpose

We performed a prospective cohort study to evaluate the effectiveness of disc synoptoscope on binocularity in patients with abnormal binocular vision.

Methods

39 eligible subjects were recruited for visual therapy with disc synoptoscope in treatment group and 38 were just observed as control.

Results

Simultaneous perception in treatment group was better than controls at 6-month visit (p < 0.05). Fusional amplitude improved in treatment group but decreased in control group at 3- and 6-months visits (p < 0.001). Near and distance stereopsis in treatment group were better than controls at 3- and 6-months (p < 0.05). The improvements of monocular and binocular acuity in treatment group were better than controls at 3- and 6-months (p < 0.05). Postoperative recurrence rate in treatment group was lower than controls (p < 0.05).

Conclusion

Visual therapy with disc synoptoscope is effective in improving short-term binocular vision for the patients with abnormal binocular vision; disc synoptoscope could serve as an effective home-based visual therapy instrument.

     

Infliximab exerts a dose-dependent effect on retinal safety in the albino rabbit

Purpose

To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance.

Methods

We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared.

Results

Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod–cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP.

Conclusions

While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod–cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam’s razor).