Goldmann Visual Field Research Articles

Leber’s Hereditary Optic Neuropathy Following Unilateral Syphilitic Optic Neuritis

This report describes a case of Leber’s hereditary optic neuropathy (LHON) following unilateral syphilitic optic neuritis. A 31-year-old man presented with a four-day history of decreased vision in his left eye. At the initial visit, the patient’s best corrected visual acuity (BCVA) was 1.2 and 0.02 in the right and left eye, respectively, along with a relative afferent pupillary defect in the left eye. Goldmann visual field testing revealed a central absolute scotoma and an enlarged blind spot in the left eye. Serological testing confirmed syphilis with rapid plasma reagin positivity. The patient was diagnosed with syphilitic optic neuritis and treated with intravenous penicillin G (24 million units daily) for two weeks. After two weeks of therapy, his left BCVA improved to 0.4 after two months. However, five months later, despite completing syphilis treatment, the patient developed acute painless visual loss in both eyes. His BCVA decreased to 0.8 and 0.05 in the right and left eyes, respectively. Goldmann visual field testing revealed a central absolute scotoma and an enlarged blind spot in both eyes. After two weeks, BCVA progressively declined to 0.4 in the right and 0.04 in the left eye. Furthermore, Goldmann visual field testing revealed an enlarged central absolute scotoma and blind spot in both eyes. Six months after the initial examination, his BCVA was counting fingers and 0.02 in the right and left eye, respectively. The optic discs appeared diffusely pale in both eyes. Genetic testing for LHON revealed a pathologic mtDNA 11778 point mutation. This case underscores the importance of considering the possibility of LHON if acute or subacute vision loss occurs subsequently or simultaneously in both eyes and remains unresponsive to treatment.

Visual Field Improvement in Non-Arteritic Posterior Ischemic Optic Neuropathy in a Patient Treated with Intravenous Steroids

A 50-year-old man presented with a nasal visual field defect in the left eye. His medical history was unremarkable. On ophthalmic examination, his best-corrected visual acuity (BCVA) was 1.2 in both eyes. Fundoscopy revealed no abnormalities in either eye. Goldmann visual field test showed a nasal visual field defect in the left eye. The patient was diagnosed with NPION of the left eye and was followed up without treatment. However, four days after the initial visit, his BCVA decreased to counting finger in the left eye. Goldmann visual field test showed a complete nasal visual field defect with central absolute scotoma. Following admission, the patient was treated for 3 days with intravenous methylprednisolone pulse therapy. Three months later, his BCVA was improved to 0.8 in the left eye, but central relative scotoma was remained. Six months later, his BCVA was maintained at 0.8, and central relative scotoma was disappeared. However, the optic disc looked diffusely pale in the left eye. This case highlights that steroid therapy is an option for severe cases with posterior ischemic optic neuropathy.

The Correlation between Body Mass Index and Intraocular pressure, Retinal Nerve Fiber Layer Thickness and Visual Field

Abstract Background Obesity has become a world-wide medical epidemic. it constitutes an important risk for several eye diseases like cataract, diabetic retinopathy, age related macular degeneration (AMD) and glaucoma.Body mass index (BMI) is one of the most specific and objective measurement to define obesity. Obesity has recently been reported to be negatively associated with visual acuity, but the ocular conditions underlying this association and the potential implications are unclear. Amongst different eye diseases, obesity has been associated with cataract, age-related maculopathy, diabetic retinopathy, and glaucoma. Purpose To investigate the relationship between BMI and IOP and correlate it with changes in RNFL thickness and visual field. Materials and Methods 60 participants divided into three groups (normal, overweight, and obese) according to BMI, were included in this Cross-Sectional Study (pilot study). Participants underwent a complete ophthalmologic assessment, measurement of RNFL thickness and ganglion cell complex (GCC) thickness using SD-OCT, IOP with Goldmann applanation tonometry (GAT) and visual field analysis using Humphrey field analyser. Results IOP was significantly higher in obese group than those in healthy weight and overweight group. Also, IOP was statistically significant higher in overweight group compared with those healthy weight group. There were no significant differences between the three groups in average, superior, inferior, nasal, and temporal RNFL thicknesses or in GCC thickness. Yet, GCC thickness in the obese group showed significant negative correlation with BMI.There were no significant differences between the three groups in MD, and VFI. Conclusion IOP was variable according to the degree of obesity with incremental pattern with advance of BMI. BMI of overweight group had no correlation with IOP, average, superior, inferior, nasal, and temporal RNFL thicknesses. While BMI of obese group showed a significant positive correlation with IOP and negative correlation with GCC thickness.

A Case of Nonarteritic Anterior Ischemic Optic Neuropathy that Recurred in the same Eye within a Month

A 78-year-old woman presented with an upper visual field defect in the left eye. On ophthalmic examination, her best-corrected visual acuity (BCVA) was 1.2 in both eyes. Fundoscopy revealed inferior optic disc swelling. Goldmann visual field test showed an upper visual field defect. The patient was diagnosed with nonarteritic anterior ischemic optic neuropathy (NAION) of the left eye and was followed up without treatment. One month after the initial visit, her BCVA decreased to 0.15 in the left eye. Fundoscopy revealed superior optic disc swelling. Goldmann visual field test showed an inferior visual field defect and central relative scotoma. Based on her clinical findings, she was diagnosed with recurrent NAION. Three months after the initial visit, her BCVA was 0.2 in the left eye, and the optic nerve developed atrophy. This case highlights the importance for clinicians to be aware of NAION recurred in the same eye within a short period of time.

A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease

PurposeTo investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution. DesignRetrospective, single institution, cohort review. SubjectsPatients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4. MethodsDNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients that shared one allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects. Main Outcome MeasuresAge of first uncorrectable vision loss, best corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field. ResultsA total of 460 patients from 390 families had convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 399 patients and partial genotypes in 61. The median age of first vision loss was 16 years (range 4-76 years). 265 of the families (68%) had a unique genotype and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a greater than 15-year difference in age of first vision loss. 241 different alleles were identified among the members of this cohort and 161 of these (67%) were found in only a single individual. ConclusionsABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before age 5 years to a late-onset RPE-based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that the majority of patients in any cohort will have a unique genotype. The latter observations taken together suggest that patients’ clinical findings will in most cases be more useful for predicting their clinical course than their genotype.

Unilateral Syphilitic Optic Neuritis without Uveitis

This report describes a case of case of unilateral syphilitic optic neuritis without uveitis. A 56-year-old man presented with complaints of four days history of decreasing vision in his left eye. At the initial visit, the patient’s best corrected visual acuity was 1.2 and 0.03 in the right and left eye, respectively. A relative afferent pupillary defect was observed in the left eye. Slit-lamp examination revealed no cells, flare or keratic precipitates in the anterior segment either eye. Fundoscopy revealed diffuse optic disc swelling with peripapillary hemorrhage in the left eye. Goldmann visual field testing identified central absolute scotoma and an enlarged blind spot in the left eye. On serological evaluation for syphilis, serum rapid plasma reagin (RPR) and treponema pallidum hemagglutination assay (TPHA) were positive (RPR 52.5, TPHA 740.0). In addition, IgM fluorescent Treponemal antibody absorbance (FTA-ABS) was positive. In contrast, cerebrospinal fluid showed negative RPR and positive TPHA (TPHA 11.8). Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis and increased protein content and glucose. Magnetic resonance imaging showed a swollen enhanced lesion in the left optic nerve. The patient was diagnosed with syphilitic optic neuritis and received the currently recommended treatment with intravenous penicillin G (PCG). Twenty-four million units per day of PCG were administered for 2 weeks. After 2 weeks of therapy, his left visual acuity improved to 0.3 in 2 months. However, the optic disc looked diffusely pale in the left eye. At 6-month visit, the patient was clinically stable. RPR turned out negative and there was a reduction in serological TPHA reactivity. We consider that it is essential to perform serological tests for syphilis in every patient with optic neuritis, which makes it possible to initially treat syphilitic optic neuritis with PCG.

Quantification of Goldmann Visual Fields During Resolution of Traumatic Optic Neuropathy

Purpose: We describe the clinical findings in a Japanese patient with unilateral traumatic optic neuropathy (TON) who underwent steroid pulse therapy followed by optic canal decompression surgery. The optic nerve function was assessed longitudinally and quantitatively by Goldmann visual fields (GVFs). This was accomplished by measuring the area of each isopter and scotoma, and the findings were compared with the visual acuities recorded during the course of the resolution of the TON.Case Presentation: A 70‐year‐old man suffered from TON in his left eye after falling from a 3 m cliff. On examination at the Saitama Medical University Hospital, his decimal best corrected visual acuity (BCVA) in his left eye was 0.2. Computed tomography revealed a fracture of the lateral wall of the left orbit, but no obvious optic canal fracture was observed. Steroid pulse therapy was started, and optic nerve decompression surgery was performed. After steroid administration, there was a slight improvement in the visual acuity, and a response in the I/3e isopter was present (area 17.76 deg2). However, the V/4e area decreased from 539.35 to 359.36 deg2. Three days after the optic canal decompression surgery, the decimal visual acuity improved to 0.6, and the V/4e area and I/3e area increased to 1122.52 and 46.88 deg2, respectively. Postoperatively, there was a marked improvement in the size of the GVFs that corresponded to the improved visual acuity. The visual acuity of the left eye was 0.8 after 6 months, and the GVF was still not completely normal.Conclusions: Our findings showed the course of recovery of the visual acuity and visual field in an eye with TON. The quantification of GVF was helpful in assessing the course of recovery after the treatments. The new quantitative index of the GVFs may be helpful in evaluating the effectiveness of treatments for optic nerve disorders.

Mutational Profile and Retinal Phenotypes of PCARE-Related Cone-Rod Dystrophies in a Mexican Cohort.

The aim of the study is to describe the genotype and phenotype of a Mexican cohort with PCARE-related retinal disease. The study included 14 patients from 11 unrelated pedigrees with retinal dystrophies who were demonstrated to carry biallelic pathogenic variants in PCARE. Visual assessment methods included best corrected visual acuity, color fundus photography, Goldmann visual field test, kinetic perimetry, dark/light adapted chromatic perimetry, full-field electroretinography, autofluorescence imaging, and spectral domain-optical coherence tomography imaging. Genetic screening was performed either by gene panel sequencing or by exome sequencing. According to the results of multimodal imaging and functional tests, all 14 patients were diagnosed with cone-rod dystrophy. Six different PCARE pathogenic alleles were identified in our cohort, including three novel mutations: c.3048_3049del (p.Tyr1016∗), c.3314_3315del (p.Ser1105∗), and c.551A > G (p.His184Arg). Notably, alleles p.His184Arg, p.Arg613∗, and p.Arg984∗ were present in 18 of the 22 (82%) PCARE alleles from probands in our cohort. Our work expands the PCARE mutational profile by identifying three novel pathogenic variants causing retinal dystrophy. While phenotypic variations occurred among patients, a cone-rod dystrophy pattern was observed in all affected individuals.

Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

Using Goldmann Visual Field Volume to Track Disease Progression in Choroideremia

Choroideremia is an X-linked choroidopathy caused by pathogenic variants in the CHM gene. It is characterized by the early appearance of multiple scotomas in the peripheral visual field that spread and coalesce, usually sparing central vision until late in the disease. These features make quantitative monitoring of visual decline particularly challenging. Here, we describe a novel computational approach to convert Goldmann visual field (GVF) data into quantitative volumetric measurements. With this approach, we analyzed visual field loss in a longitudinal, retrospective cohort of patients with choroideremia. Single-center, retrospective, cohort study. We analyzed data from 238 clinic visits of 56 molecularly-confirmed male patients with choroideremia from 41 families (range, 1-27 visits per patient). Patients had a median follow up of 4 years (range, 0-56 years) with an age range of 5 to 76 years at the time of their visits. Clinical data from molecularly-confirmed patients with choroideremia, including GVF data, were included for analysis. Goldmann visual fieldrecords were traced using a tablet-based application, and the 3-dimensional hill of vision was interpolated for each trace. This procedure allowed quantification of visual field loss from data collected over decades with differing protocols, including different or incomplete isopters. Visual acuity (VA) data were collected and converted to logarithm of the minimum angle of resolution values. A delayed exponential mixed-effects model was used to evaluate the loss of visual field volume over time. Visual acuity and GVF volume. The estimated mean age at disease onset was 12.6 years (standard deviation, 9.1 years; 95% quantile interval, 6.5-36.4 years). The mean field volume loss was 6.8% per year (standard deviation, 4.5%; 95% quantile interval, 1.9%-18.8%) based on exponential modeling. Field volume was more strongly correlated between eyes (r2=0.935) than best-corrected VA (r2=0.285). Volumetric analysis of GVF data enabled quantification of peripheral visual function in patients with choroideremia and evaluation of disease progression. The methods presented here may facilitate the analysis of historical GVF data from patients with inherited retinal disease and other diseases associated with visual field loss. This work informs the creation of appropriate outcome measures in choroideremia therapeutic trials, particularly in trial designs. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Single Center Experience with Voretigene Neparvovec Gene Augmentation Therapy in RPE65 Mutation–Associated Inherited Retinal Degeneration in a Clinical Setting

To assess the impact of baseline data on psychophysical and morphological outcomes of subretinal voretigene neparvovec (VN) (Luxturna, Spark Therapeutics, Inc.) treatment. Single-center, retrospective, longitudinal, consecutive case series. Patients with RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) treated between February 2020 and March 2022 with VN and oral immunosuppression according to the manufacturer's recommendation by one surgeon (F.G.H.). Retrospective analysis of surgical and clinical records, ancillary testing, and retinal imaging after VN therapy for RPE65-IRD. Descriptive statistics compared data at baseline up to 32 months post-treatment. Best-corrected visual acuity (BCVA), low-luminance VA (LLVA), Goldmann visual fields (GVFs), chromatic full-field stimulus threshold (FST) testing (FST), scotopic and photopic 2-color threshold perimetry (2CTP), and multimodal retinal imaging. Thirty eyes of 19 patients were analyzed (10 pediatric patients < 20 years; 20 adult patients > 20 years of age; overall range: 8-40 years) with a median follow-up of 15 months (range, 1-32). The fovea was completely or partially detached in 16 eyes, attached in 12 eyes, and not assessable in 2 eyes on intraoperative imaging. Median BCVA at baseline was better in the pediatric group (P < 0.05) and did not change significantly independent of age. Meaningful loss of BCVA (≥ 0.3 logarithm of the minimal angle of resolution [logMAR]) occurred in 5 of 18 adult eyes, and a meaningful gain (≥-0.3 logMAR) occurred in 2 of 18 adult and 2 of 8 pediatric eyes. The LLVA and scotopic 2CTP improved considerably in pediatric patients. Scotopic blue FST improved at all ages but more in pediatric patients (8/8 eyes gained ≥ 10 decibels [dB]; P < 0.05). In pediatric patients, median GVF improved by 20% for target V4e and by 50% for target III4e (target I4e not detected). Novel atrophy developed in 13 of 26 eyes at the site of the bleb or peripheral of vascular arcades. Improvements in FST did not correlate with development of chorioretinal atrophy at 12 months. Mean central retinal thickness was 165.87 μm (± 26.26) at baseline (30 eyes) and 157.69 μm (± 30.3) at 12 months (26 eyes). Eight adult patients were treated unilaterally. The untreated eyes did not show meaningful changes during follow-up. These data in a clinical setting show the effectiveness of VN therapy with stable median BCVA and mean retinal thickness and improvements of LLVA, FST, and 2CTP up to 32 months. Treatment effects were superior in the pediatric group. We observed new chorioretinal atrophy in 50% of the treated eyes. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluation of Cup Disc Ratio and RNFL Thickness Based on Goldmann Visual Field Test

Introduction and Objective : To assess the relationship between the cup-disc ratio of the optic nerve head and peripapilarry RNFL thickness to the visual field loss in glaucoma patients. Methods : Visual field from Goldmann kinetic perimerty and Ocular Computed Tomography (OCT) records from Yap Eye Hospital, Yogyakarta are used to examine the figure of visual field loss in glaucoma patient. Result: Broad spectrum of glaucoma-related visual field defects were observed from 73 eyes. The most common visual field defects are arcuate defect (23.3%) and followed by general depression. Arcuate defects can already observable in some patients with cup-disk ratio of 0.5 (30%).Arcuate defect occurs in the average RNFL thickness of 69.90 ?m (46.93-118.77). It appears that the pinhole vision appeared on the average RNFL thickness of 44.23 ?m (25.33-63.13), and temporal RNFL thickness remnant occured at 48.64 ?m (46.22-51.06). RNFL thickness with normal visual field was on the thickness of 107.78 ?m (100.27-115.29). Conclusion: Visual field defect that may be observed in glaucoma with Goldmann kinetic perimetry are arcuate defect, and general visual field depression. RNFL thickness may be correlated longitudinally with the worsening of visual field defect.

Ultrasound Cyclo Plasty in Patients with Open Angle Glaucoma and High Myopia.

Ultrasound cyclo plasty (UCP) using high-intensity focused ultrasound is an effective and safe procedure in lowering intraocular pressure (IOP) in patients with glaucoma, even in those with high myopia. This study aimed to evaluate the efficacy and safety of UCP in glaucoma patients with high myopia. In this retrospective, single-center study, we enrolled 36 eyes divided into 2 groups based on axial length: group A (≥26.00mm) and group B (<26.00mm). We collected data about visual acuity, Goldmann applanation tonometry, biomicroscopy, and visual field before the procedure and at 1, 7, 30, 60, 90, 180, and 365 days after the procedure. Mean IOP significantly decreased in both groups after treatment ( P <0.001). Mean IOP reduction from baseline to the last visit was 9.8±6.6mmHg (38.7%) in group A and 9.6±6.3mmHg (34.8%) in group B ( P <0.001). Mean IOP at the last visit was 15.8±4.1mmHg in the myopic group and 18.1±5.6mmHg in the non-myopic one. Regarding the number of IOP-lowering eyedrops being taken by our patients, statistically significant differences were found between groups A and B neither at baseline (2.8±0.9 and 2.6±1.0; P =0.568) nor 1 year after the procedure (2.5±1.1 and 2.6±1.1; P =0.762). No major complications occurred. All minor adverse events resolved within a few days. UCP seems to be an effective and well-tolerated strategy to lower IOP in glaucoma patients with high myopia.

Optic disc hemorrhage in a young female following mRNA coronavirus disease 2019 vaccination: a case report

Since the development of the coronavirus disease 2019 vaccine, there have been many reports of its adverse effects. While respiratory symptoms are common, many other symptoms in various organs have been reported. Herein, we report a case of optic disc and retinal hemorrhage that developed immediately after coronavirus disease 2019 vaccination. A healthy 18-year-old Japanese female noticed floater in the left eye 1day after the second vaccination for coronavirus disease 2019 (Pfizer Inc.). Her visual acuity was 20/20 in the left eye, and Goldmann visual field test showed a relative scotoma around blind spot and in the temporal lower quadrant. It was considered due to subretinal hemorrhage and optic disc swelling. Fundus examination revealed retinal and optic disc hemorrhage. Pupillary reflex was intact and central critical flicker was not impaired, indicating that optic nerve was not involved. There was no sign of inflammation, vascular abnormality, nor history of an intense Valsalva maneuver. The hemorrhage resolved spontaneously within 5months. This case expands the clinical presentation of coronavirus disease 2019 vaccination-associated ocular adverse events, and it should be kept in mind when patients with similar symptoms visit clinics. The case report will help clinicians avoid unnecessary and invasive examinations and treatment.

Detection of visual field defects using Eye Movement Pediatric Perimetry in children with intracranial lesions: feasibility and applicability

The study aimed at evaluating the feasibility of Eye Movement Pediatric Perimetry (EMPP) among children in detecting Visual Field Defects (VFDs) associated with Intracranial Lesions (IL). Healthy controls (n = 35) and patients diagnosed with IL (n = 19) underwent a comprehensive clinical evaluation followed by a Goldmann Visual Field (GVF) and a customised EMPP protocol. During EMPP, all the participants were encouraged to fixate on a central target and initiate Saccadic Eye Movement (SEM) responses towards randomly appearing peripheral stimuli. The SEM responses were recorded using an eye-tracking device and further inspected to calculate Performance Scores (PS), Saccadic Reaction Times (SRTs), and an EMPP Index (EMPI). The mean age (years) of the controls and cases were 7.3 (SD: 1.5) and 9.4 (SD: 2.4) respectively. Among the controls, the older children (≥7 years) showed statistically significantly faster SRTs (p = 0.008) compared to the younger group. The binocular EMPP measurements compared between the controls and the cases revealed no statistically significant differences in PS (p = 0.34) and SRT (p = 0.51). EMPP failed in 4 children because of data loss or unacceptably poor PS whereas GVF failed in 7 children due to unreliable subjective responses. Of the 16 reports, with regard to the central 30-degree VF, 63% of the outputs obtained from both methods were comparable. EMPP is a reliable method to estimate and characterise the central 30-degree VF in greater detail in children with IL. EMPP can supplement the conventional methods, especially in those children who fail to complete a long duration GVF test.

Phenotypic and Genetic Characteristics in a Cohort of Patients with Usher Genes.

Background: This study aimed to compare phenotype–genotype correlation in patients with Usher syndrome (USH) to those with autosomal recessive retinitis pigmentosa (NS-ARRP) caused by genes associated with Usher syndrome. Methods: Case notes of patients with USH or NS-ARRP and a molecularly confirmed diagnosis in genes associated with Usher syndrome were reviewed. Phenotypic information, including the age of ocular symptoms, hearing impairment, visual acuity, Goldmann visual fields, fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (OCT) imaging, was reviewed. The patients were divided into three genotype groups based on variant severity for genotype-phenotype correlations. Results: 39 patients with Usher syndrome and 33 patients with NS-ARRP and a molecular diagnosis in an Usher syndrome-related gene were identified. In the 39 patients diagnosed with Usher syndrome, a molecular diagnosis was confirmed as follows: USH2A (28), MYO7A (4), CDH23 (2), USH1C (2), GPR98/VLGR1 (2) and PCDH15 (1). All 33 patients with NS-ARRP had variants in USH2A. Further analysis was performed on the patients with USH2A variants. USH2A patients with syndromic features had an earlier mean age of symptom onset (17.9 vs. 31.7 years, p < 0.001), had more advanced changes on FAF imaging (p = 0.040) and were more likely to have cystoid macular oedema (p = 0.021) when compared to USH2A patients presenting with non-syndromic NS-ARRP. Self-reported late-onset hearing loss was identified in 33.3% of patients with NS-ARRP. Having a syndromic phenotype was associated with more severe USH2A variants (p < 0.001). Eighteen novel variants in genes associated with Usher syndrome were identified in this cohort. Conclusions: Patients with Usher syndrome, whatever the associated gene in this cohort, tended to have an earlier onset of retinal disease (other than GPR98/VLGR1) when compared to patients presenting with NS-ARRP. Analysis of genetic variants in USH2A, the commonest gene in our cohort, showed that patients with a more severe genotype were more likely to be diagnosed with USH compared to NS-ARRP. USH2A patients with syndromic features have an earlier onset of symptoms and more severe features on FAF and OCT imaging. However, a third of patients diagnosed with NS-ARRP developed later onset hearing loss. Eighteen novel variants in genes associated with Usher syndrome were identified in this cohort, thus expanding the genetic spectrum of known pathogenic variants. An accurate molecular diagnosis is important for diagnosis and prognosis and has become particularly relevant with the advent of potential therapies for Usher-related gene

Clinical-genetic findings in a group of subjects with macular dystrophies due to mutations in rare inherited retinopathy genes.

To describe the results of clinical and molecular analyses in a group of patients suffering from inherited macular dystrophies, in which next-generation sequencing (NGS) efficiently detected rare causative mutations. A total of eight unrelated Mexican subjects with a clinical and multimodal imaging diagnosis of macular dystrophy were included. Visual assessment methods included best corrected visual acuity, color fundus photography, Goldmann visual field tests, kinetic perimetry, dark/light adapted chromatic perimetry, full-field electroretinography, autofluorescence imaging, and spectral domain-optical coherence tomography imaging. Genetic screening was performed by means of whole exome sequencing with subsequent Sanger sequencing validation of causal variants. All patients exhibited a predominantly macular or cone-dominant disease. Patients' ages ranged from 12 to 60years. Three cases had mutations in genes associated with autosomal dominant inheritance (UNC119 and PRPH2) while the remaining five cases had mutations in genes associated with autosomal recessive inheritance (CNGA3, POC1B, BEST1, CYP2U1, and PROM1). Of the total of 11 different pathogenic alleles identified, three were previously unreported disease-causing variants. Macular dystrophies can be caused by defects in genes that are not routinely analyzed or not included in NGS gene panels. In this group of patients, whole exome sequencing efficiently detected rare genetic causes of hereditary maculopathies, and our findings contribute to expanding the current knowledge of the clinical and mutational spectrum associated with these disorders.

Unilateral Retinitis Pigmentosa Associated with Possible Ciliopathy and a Novel Mutation.

Unilateral retinitis pigmentosa (URP) is a rare retinal dystrophy. We describe the clinical course of two patients with (URP) unilateral retinitis pigmentosa confirmed by genetic testing, indicating ciliary dysfunction. Methods: The methods used in this study included a detailed ophthalmic examination, multimodal retinal imaging, Goldmann visual fields, full-field electroretinography (ffERG) and targeted next-generation sequencing. Results: A 32-year-old female (patient 1) and 65-year-old male (patient 2) were found to have URP. ffERG showed a non-recordable response in the affected eye and a response within normal limits in the fellow eye of patient 1, while patient 2 showed non-recordable responses in the apparently unaffected eye and a profound reduction in the photopic and scotopic responses in the affected eye. Next-generation sequencing revealed novel compound heterozygous c.373 C>T (p.Arg125Trp) and c.730-22_730-19dup variants in AGBL5 in patient 1, and a novel hemizygous c.1286 C>T (p.Pro429Leu) in patient 2; both gene mutations were 0%. Segregation analysis was not possible for either of the mutations. Conclusion: This report expands the clinical and molecular genetic spectrum of URP.

Retinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort.

PurposeBiallelic variants in CLRN1 are responsible for Usher syndrome 3A and non-syndromic rod–cone dystrophy (RCD). Retinal findings in Usher syndrome 3A have not been well defined. We report the detailed phenotypic description of RCD associated with CLRN1 variants in a prospective cohort.MethodsPatients were clinically investigated at the National Reference Center for rare ocular diseases at the Quinze-Vingts Hospital, Paris, France. Best-corrected visual acuity (BCVA) tests, Goldmann perimetry, full-field electroretinography (ffERG), retinal photography, near-infrared reflectance, short-wavelength and near-infrared autofluorescence, and optical coherence tomography (OCT) were performed for all patients.ResultsFour patients from four unrelated families were recruited. Mean follow-up was 11 years for three patients, and only baseline data were available for one subject. Median BCVA at baseline was 0.2 logMAR (range, 0.3–0). ffERG responses were undetectable in all subjects. The III4e isopter of the Goldmann visual field was constricted to 10°. The retinal phenotype was consistent in all patients: small whitish granular atrophic areas were organized in a network pattern around the macula and in the midperiphery. OCT showed intraretinal microcysts in all patients. Upon follow-up, all patients experienced a progressive BCVA loss and further visual field constriction. Four distinct pathogenic variants were identified in our patients: two missense (c.144T>G, p.(Asn48Lys) and c.368C>A, p.(Ala123Asp)) and two frameshift variants (c.176del, p.(Gly59Valfs*13) and c.230dup, p.(Ala78Serfs*52)).ConclusionsRCD in Usher 3A syndrome has some distinctive features. It is a severe photoreceptor dystrophy with whitish granular posterior pole appearance and cystic maculopathy.

Dominant Optic Atrophy Caused by the c.1334G&gt;A Mutation of the OPA1 Gene

Purpose: Dominant optic atrophy is one of the most common hereditary optic neuropathies, causing progressive bilateral vision loss that begins early in life. Optic atrophy 1 (OPA1) gene mutation brings about mitochondrial dysfunction, which results in clinical manifestations of dominant optic atrophy. Here, we report a case of dominant optic atrophy caused by the c.1334G&gt;A mutation of the OPA1 gene, the first known case in Korea to our knowledge.Case summary: A 12-year-old female patient with no specific medical history or systemic symptoms visited our clinic complaining of a progressive decrease in vision in either eye. Slit-lamp microscopy, intraocular pressure, ocular motility, and pupil reflex were normal. However, her best-corrected visual acuity in both eyes was 20/100, and her color vision was reduced to 8/12 in Ishihara’s test. Fundus examination showed temporal pallor of the optic nerve head in both eyes, and a corresponding cecocentral scotoma was observed on Goldmann visual field examination. Optical coherence tomography revealed significant thinning of the peripapillary retinal fiber layer and macular ganglion cell layer in both eyes. Genetic examination confirmed the c.1334G&gt;A mutation of the OPA1 gene.Conclusions: We report a case of dominant optic nerve atrophy caused by c.1334G&gt;A mutation of the OPA1 gene and its clinical manifestations.