Deep neurological phenotyping in oculo-dento-digital syndrome.

OBJECTIVES: Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant congenital malformation syndrome characterized by high penetrance and great phenotypic heterogeneity. Neurological manifestations are thought to occur in about one third of cases, but systematic studies are not available. We performed deep neurological phenotyping of 10 patients in one ODDD pedigree. METHODS: Retrospective case series. We analyzed in depth the neurological phenotype of a three-generation family segregating the heterozygous c.416 T > C, p.(Ile139Thr) in GJA1. Clinical and neuroradiological features were retrospectively evaluated. Brain MRI and visual evoked potentials were performed in 8 and 6 cases, respectively. RESULTS: Central nervous system manifestations occurred in 5 patients, the most common being isolated ataxia either in isolation or combined with spasticity. Furthermore, sphincteric disturbances (neurogenic bladder and fecal incontinence) were recognized as the first manifestation in most of the patients. Subclinical electrophysiological alteration of the optic pathway occurred in all the examined patients. Neuroimaging was significant for supratentorial hypomyelination pattern and hyperintense superior cerebellar peduncle in all examined patients. CONCLUSION: The neurological involvement in ODDD carriers is often missed but peculiar clinical and radiological patterns can be recognized. Deep neurological phenotyping is needed to help untangle ODDD syndrome complexity and find genotype-phenotype correlations.

VASCULAR PERFUSION DENSITY MAPPING USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY COMPARING NORMAL AND OPTIC DISK PIT EYES.

PURPOSE: Optic disk pits (ODPs) are typically detected incidentally as small, gray, unilateral, oval-shaped excavation in the temporal optic disk on routine fundus examination. In this cross-sectional retrospective case series, we report optical coherence tomography angiography findings in patients with unilateral ODPs and describe changes in vessel perfusion associated with ODP. METHODS: A total of eight eyes (four with ODP and four normal contralateral) were included in this study. Patients were excluded if any other optic disk abnormalities were present. Spectral-domain optical coherence tomography angiography (AngioVue; Optovue, Fremont, CA) imaging was conducted to map the vascularization of three layers in the optic nerve over a 4.5-mm × 4.5-mm region. The radial peripapillary capillaries, the nerve head capillaries, and the choriocapillaris were automatically segmented based on the OCT system software, and the capillary perfusion density (CPD) was quantified for each layer. Kruskal-Wallis one-way analysis of variance was used to compare CPD in normal and ODP eyes of four patients with monocular ODP. RESULTS: Overall, CPD was lower in eyes with ODP compared with the contralateral normal eye in the radial peripapillary capillary (0.4521 ± 0.08 vs. 0.5505 ± 0.03, P = 0.08) and nerve head capillary layers (0.5461 ± 0.08 vs. 0.5989 ± 0.01, P = 0.08). Significantly lower CPD values were associated with ODP eyes in the radial peripapillary capillary layer within the disk (P = 0.04), inferior nasal (P = 0.04), and temporal (P = 0.02) regions and in the nerve head vessel layer within the disk region (P = 0.04). Significantly higher CPD values were associated with ODP eyes in the choriocapillaris layer within the nasal (P = 0.02), superior temporal (P = 0.02), and inferior temporal (P = 0.02) regions. Visual acuity was also decreased in ODP eyes at 0.4 ± 0.3 logarithm of the minimum angle of resolution units (20/50) compared with normal eyes at 0.1 ± 0.1 logarithm of the minimum angle of resolution units (20/25) (P = 0.12). CONCLUSION: This study demonstrated that the presence of an ODP is associated with decreased vascular density in some regions of the optic disk and reduced visual acuity.

Compound heterozygous ADAMTS9 variants in Joubert syndrome-related disorders without renal manifestation.

BACKGROUND: Ciliopathies are the outcomes of defects of primary cilia structures and functions which cause multisystemic developmental disorders, such as polycystic kidney disease, nephronophthisis, retinitis pigmentosa, Joubert syndrome (JS), and JS-related disorders (JSRD) with additional organ involvement including oral-facial-digital syndrome and so on. They often share common and unexpected phenotypic features. CASE PRESENTATION: We report a 4-year-old-boy case with compound heterozygous variants of ADAMTS9. Unlike the cases with ADAMTS9 variants in the previous report, which identified that homozygous variants of ADAMTS9 were responsible for nephronophthisis-related ciliopathies in two cases, the current case did not have nephronophthisis nor renal dysfunction, and his clinical features, such as oculomotor apraxia, hypotonia, developmental delay, bifid tongue, and mild hypoplasia of cerebellar vermis indicated JSRD. CONCLUSIONS: The case suggested a possible association between the clinical presentation of JSRD and ADAMTS9-related disease, and it shows a wide spectrum of ADAMTS9 phenotype.

Association of Birth Weight With Foveolar Thickness in Adulthood: Results From a Population-Based Study.

Purpose: Low birth weight (BW) is associated with alterations of foveal shape development in childhood-leading to an increased retinal thickness of the fovea. The aim of the present study was to assess whether BW has a long-term effect on foveal retinal thickness (RT) and is still present in adulthood. Methods: In the German population-based Gutenberg Health Study (GHS), participants were examined with spectral-domain optical coherence tomography. The association between self-reported BW and RT in the foveolar and perifoveal locations was assessed. Multivariable linear regression analyses with adjustment for potential confounders and grading of foveal hypoplasia were performed. Results: Overall, RT measurements and self-reported BW were available for 2,539 participants (1300 female, mean age 54.5 ± 9.7 years). The absolute foveolar RT was 239.6 ± 25.8 µm, 232.2 ± 20.1 µm and 234.8 ± 21.0 µm, respectively, in the low (<2500 g), normal (2500-4000 g) and high (>4000 g) BW groups (P < 0.001). After adjustment for confounders, an association was observed between lower BW and increased foveolar thickness (B = -0.35 [95% confidence interval {CI}: -0.49; -0.20] µm/100 g; P < 0.001), whereas only a weak association with RT was observed with the nasal (P = 0.010), temporal (P = 0.011), and inferior (P = 0.021) quadrants in the 1 mm distance, with no association in the 2 mm distance to the fovea. Foveal hypoplasia grade 1 was more frequent in the low BW group (6.8%) compared to the normal (0.9%) and high BW group (1.2%). Conclusions: This study provides evidence of an association between lower BW and increased foveolar thickness and foveal hypoplasia, indicating that prenatal growth may affect macular morphology, which in turn may persist until adulthood and predispose to retinal disease later in life.

Penetrating Keratoplasty in Infants With Peters Anomaly: Visual and Graft Outcomes.

PURPOSE: To determine the prevalence of survival of corneal grafts and visual outcomes of primary penetrating keratoplasty (PK) in infants with Peters anomaly (PA) in Beijing, China. METHODS: Twenty-nine patients (37 eyes) with PA who underwent PK before the age of 1 year were included. Optical correction for all eyes and occlusion therapy of amblyopia for a unilateral opacity were performed 2 weeks after suture removal. All infants underwent assessment of visual acuity after surgery using Teller Acuity Cards. Survival probabilities were estimated using the Kaplan-Meier method and log-rank test. Visual outcomes and prognosis factors were analyzed using the χ2 test. RESULTS: The mean age of 29 infants undergoing primary PK was 5.7 ± 2.3 months. The mean follow-up duration was 18.0 ± 3.0 months. Twenty-seven (73.0%) of 37 grafts retained full clarity at final follow-up. Visual acuity above ambulatory was achieved in 67.6% (25/37) and >20/260 was achieved in 48.6% (18/37) of cases. Of all surgical indications, vascularized PA I (50.0%, 6/12) and PA II (18.2%, 2/11) showed a lower proportion achieving visual acuity >20/260 than nonvascularized PA I (71.4%, 10/14) (P = 0.030 < 0.05). There was no significant difference in the prevalence of graft survival and vision outcome between infants younger than 6 months and older than >6 months. CONCLUSIONS: For infants with PA who underwent PK, the prevalence of graft survival and visual acuity were related mainly to the indication. The main risk factors were corneal vascularization and an abnormal lens.

[Congenital ocular anomalies at the University Hospital Campus in Lomé, Togo]. / Les anomalies congénitales oculaires au Centre Hospitalier Universitaire-Campus de Lomé, Togo.

INTRODUCTION: congenital ocular anomalies are rare clinical entities. The purpose of this study is to describe the epidemiological and clinical features of congenital ocular anomalies at the University Hospital Campus in Lomé. METHODS: we conducted a retrospective study at the Department of Ophthalmology of the University Hospital Campus in Lomé, over a 3-year period, from January 2016 to December 2018. It involved children with congenital ocular anomalies. The study variables were: sex; age at diagnosis; type of congenital ocular anomalies; laterality. RESULTS: out of 2621 children assessed during the study period, 103 (3.9%) had congenital ocular anomalies. Of these, 60 (58.2%) were boys and 43 (41.8%) girls. The average age at diagnosis was 16 ± 5.2 months (ranging from 1 months to 5 years). The most common congenital ocular anomaly was cataract (53.4%). Unilateral alterations were predominant (56.3%). Congenital ocular anomalies were isolated (82.5%); associated with systemic anomalies (11.7%); associated with each other (5.8%). CONCLUSION: these results show that the epidemiological and clinical features of congenital ocular anomalies are similar to those reported in the literature. However, in our Hospital, the frequency of congenital ocular anomalies and patients' age at diagnosis are high. Early diagnosis is essential to ensure adequate management and preserve visual function.

The Transition Zone Protein AHI1 Regulates Neuronal Ciliary Trafficking of MCHR1 and Its Downstream Signaling Pathway.

The Abelson-helper integration site 1 (AHI1) gene encodes for a ciliary transition zone localizing protein that when mutated causes the human ciliopathy, Joubert syndrome. We prepared and examined neuronal cultures derived from male and female embryonic Ahi1+/+ and Ahi1-/- mice (littermates) and found that the distribution of ciliary melanin-concentrating hormone receptor-1 (MchR1) was significantly reduced in Ahi1-/- neurons; however, the total and surface expression of MchR1 on Ahi1-/- neurons was similar to controls (Ahi1+/+). This indicates that a pathway for MchR1 trafficking to the surface plasma membrane is intact, but the process of targeting MchR1 into cilia is impaired in Ahi1-deficient mouse neurons, indicating a role for Ahi1 in localizing MchR1 to the cilium. Mouse Ahi1-/- neurons that fail to accumulate MchR1 in the ciliary membrane have significant decreases in two downstream MchR1 signaling pathways [cAMP and extracellular signal-regulated kinase (Erk)] on MCH stimulation. These results suggest that the ciliary localization of MchR1 is necessary and critical for MchR1 signaling, with Ahi1 participating in regulating MchR1 localization to cilia, and further supporting cilia as critical signaling centers in neurons.SIGNIFICANCE STATEMENT Our work here demonstrates that neuronal primary cilia are powerful and focused signaling centers for the G-protein-coupled receptor (GPCR), melanin-concentrating hormone receptor-1 (MCHR1), with a role for the ciliary transition zone protein, Abelson-helper integration site 1 (AHI1), in mediating ciliary trafficking of MCHR1. Moreover, our manuscript further expands the repertoire of cilia functions on neurons, a cell type that has not received significant attention in the cilia field. Lastly, our work demonstrates the significant influence of ciliary GPCR signaling in the overall signaling of neurons.

INVERTED INTERNAL LIMITING MEMBRANE-FLAP TECHNIQUE FOR OPTIC DISK PIT MACULOPATHY: MORPHOLOGIC AND FUNCTIONAL ANALYSIS.

PURPOSE: To analyze morphologic and functional changes after inverted internal limiting membrane-flap technique for optic disk pit maculopathy using optical coherence tomography, multifocal electroretinography, and microperimetry. METHODS: One case report. RESULTS: A 30-year-old woman presented us with decreased visual acuity (20/63) in the left eye because of retinoschisis and serous macular detachment associated with optic disk pit. Optical coherence tomography did not localize the source of intraretinal and subretinal fluid. A partial flattening of serous detachment after vitrectomy with internal limiting membrane peeling, inverted internal limiting membrane-flap technique, and gas tamponade was reported. Visual acuity and multifocal electroretinography improved while retinal sensitivity decreased at microperimetry during 3 months of follow-up. CONCLUSION: Optical coherence tomography is helpful to assess the effectiveness of surgical maneuvers to treat optic disk pit maculopathy. Multifocal electroretinography and microperimetry might offer additional tools for follow-up analysis of retinal function after surgery.

Ciliopathies and the Kidney: A Review.

Primary cilia are specialized sensory organelles that protrude from the apical surface of most cell types. During the past 2 decades, they have been found to play important roles in tissue development and signal transduction, with mutations in ciliary-associated proteins resulting in a group of diseases collectively known as ciliopathies. Many of these mutations manifest as renal ciliopathies, characterized by kidney dysfunction resulting from aberrant cilia or ciliary functions. This group of overlapping and genetically heterogeneous diseases includes polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome as the main focus of this review. Renal ciliopathies are characterized by the presence of kidney cysts that develop due to uncontrolled epithelial cell proliferation, growth, and polarity, downstream of dysregulated ciliary-dependent signaling. Due to cystic-associated kidney injury and systemic inflammation, cases result in kidney failure requiring dialysis and transplantation. Of the handful of pharmacologic treatments available, none are curative. It is important to determine the molecular mechanisms that underlie the involvement of the primary cilium in cyst initiation, expansion, and progression for the development of novel and efficacious treatments. This review updates research progress in defining key genes and molecules central to ciliogenesis and renal ciliopathies.

Adult Chinese twins with Kenny-Caffey syndrome type 2: A potential age-dependent phenotype and review of literature.

Kenny-Caffey syndrome (KCS) type 2 (OMIM 127000) is a rare syndromic cause of hypoparathyroidism which is characterized by proportionate short stature, long bone abnormalities, delayed closure of anterior fontanelle, eye abnormalities, and normal intelligence. It is caused by variants in FAM111A (NM_001942519.1). In this review, we reported the first Chinese patients, a pair of monozygotic twins, with genetically confirmed KCS type 2 with over 20 years follow-up. We summarized the clinical features of 14 previously reported and genetically confirmed KCS type 2 patients; our twin patients exhibited a unique spinal manifestation which could be an important age-dependent feature of KCS type 2. In this review, over 60% KCS type 2 patients had dental problem and over 80% suffered from refractive errors or structural eye abnormalities. Therefore, early dental, ophthalmological, and orthopedic assessments are warranted for KCS type 2 patients. Micro-orchidism, previously reported in KCS type 2 patients, was also detected in our patients. The possibility of subfertility should be considered in male KCS type 2 patients. A multidisciplinary management approach for this rare syndrome is recommended.

Long-Term Visual Outcomes and Clinical Course of Patients With Peters Anomaly.

PURPOSE: To present long-term clinical and visual outcomes of patients with Peters anomaly. METHODS: The charts of all patients diagnosed with Peters anomaly from January 2000 to December 2012 were reviewed retrospectively. Peters anomaly was classified as type I (with no lens involvement) or type II (presence of keratolenticular adhesions or cataract), with further severity grading to mild, moderate, and severe disease depending on corneal opacity location and size. Mild cases were observed. Moderate cases were managed with pupillary dilation either pharmacologically or surgically. Penetrating keratoplasty (PKP) was reserved for more severe opacity. The main outcome measures were final best spectacle-corrected visual acuity (BSCVA), incidence of glaucoma, graft survival, and nystagmus rates. RESULTS: Sixty eyes of 40 patients were included in the study. The median age of patients at presentation was 0.5 ± 20.7 months (range, 0.0-111.0 months), with a mean follow-up time of 75.8 ± 52.9 months (range, 12.1-225.3 months). Overall, final best spectacle-corrected visual acuity ranged from 0.1 logMAR to no light perception with 33 eyes (55.9%) achieving vision of 1.0 logMAR or better. Clear grafts at the last follow-up were obtained in 67.6% (25/37) of transplanted eyes, 76.0% (19/25) in Peters type I, and 50.0% (6/12) in Peters type II (P = 0.11). The probability of a clear graft at 10 years was 74.2% and 38.9% for type I and type II, respectively. Glaucoma was diagnosed in 33.3% eyes, 90.0% of which occurred after PKP. Nystagmus was highly associated with PKP intervention, occurring in 81.1% (30/37) of eyes undergoing PKP compared with 34.8% (8/23) of eyes with no PKP (P = 0.0003). CONCLUSIONS: Visual rehabilitation in Peters anomaly remains a challenge, but outcomes can be optimized using a comprehensive clinical management algorithm according to disease severity.

Interpreting the pathogenicity of Joubert syndrome missense variants in Caenorhabditis elegans.

Ciliopathies are inherited disorders caused by defects in motile and non-motile (primary) cilia. Ciliopathy syndromes and associated gene variants are often highly pleiotropic and represent exemplars for interrogating genotype-phenotype correlations. Towards understanding disease mechanisms in the context of ciliopathy mutations, we have used a leading model organism for cilia and ciliopathy research, Caenorhabditis elegans, together with gene editing, to characterise two missense variants (P74S and G155S) in mksr-2/B9D2 associated with Joubert syndrome (JBTS). B9D2 functions within the Meckel syndrome (MKS) module at the ciliary base transition zone (TZ) compartment and regulates the molecular composition and sensory/signalling functions of the cilium. Quantitative assays of cilium/TZ structure and function, together with knock-in reporters, confirm that both variant alleles are pathogenic in worms. G155S causes a more severe overall phenotype and disrupts endogenous MKSR-2 organisation at the TZ. Recapitulation of the patient biallelic genotype shows that compound heterozygous worms phenocopy worms homozygous for P74S. The P74S and G155S alleles also reveal evidence of a very close functional association between the B9D2-associated B9 complex and MKS-2/TMEM216. Together, these data establish C. elegans as a model for interpreting JBTS mutations and provide further insight into MKS module organisation. This article has an associated First Person interview with the first author of the paper.

Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis.

Purpose: Obstruction of the tear drainage causes a range of ocular surface disorders. Hitherto, the genetics of tear duct development and obstruction has been scarcely explored, and related animal models are lacking. This study aims to study the potential role of the Wnt/PCP pathway mediated by Prickle 1 in tear duct development and diseases. Methods: A severe hypomorphic Prickle 1 mutant was generated. Histology and immunohistochemistry were performed to compare wild type, Prickle 1 hypomorphic, and null mutant tear ducts. In situ hybridization was conducted to identify the signaling components in the developing tear ducts. Three-dimensional (3D) reconstruction was used to detect the human embryonic tear duct. Results: Here, we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to the blockage of the tear drainage by incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (LC), which also causes precocious eyelid opening. We observed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. An investigation of the expression of Wnt/PCP core genes demonstrated a subset of PCP signaling components expressed in the developing tear duct. Furthermore, Prickle 1 is not required for the expression of Fgfr2/Fgf10 and p63 genes, which are associated with the NLD and LC hypoplasia in humans. Last, we showed that Prickle 1 expression in the developing tear drainage system is conserved between mice and humans. Conclusions: The study suggests that malformed tear ducts caused by disruption of Prickle 1 underlies the epiphora and precocious eyelid opening.

A large deletion spanning PITX2 and PANCR in a Chinese family with Axenfeld-Rieger syndrome.

Purpose: To identify the genetic cause in a four-generation Chinese family with Axenfeld-Rieger syndrome (ARS). Methods: The family members received clinical examinations of the eye, tooth, periumbilical skin, and heart. Sanger sequencing and whole-exome sequencing (WES) were performed to screen potential mutations. The genomic deletion region around the PITX2 gene was estimated from single nucleotide polymorphism (SNP) data from WES and then confirmed with "quantitative PCR (qPCR) using a set of primers. The DNA breakpoint was further identified with long-range PCR and Sanger sequencing. Results: Symptoms including anterior segment dysplasia of the eye (iris dysplasia, multiple pupils, and posterior embryotoxon), dental dysplasia, and periumbilical skin redundancy were present in all of the affected individuals. Three of them had glaucoma. Corneal abnormalities (inferior sclerocornea, corneal endothelial dystrophy, and central corneal scar) were seen in most of the affected individuals. Cataract, limited eye movement, electrocardiographic abnormalities, intellectual disability, and recurrent miscarriages were observed in some of the affected individuals. No mutations in the coding and exon-intron adjacent regions of the PITX2 and FOXC1 genes were identified with Sanger sequencing. According to the SNP data from WES, we suspected that there might be a deletion region (at most 1.6 Mb) around the PITX2 gene. With the use of qPCR and long-range PCR, we identified a 53,840 bp deletion (chr4: 111,535,454-111,588,933) spanning PITX2 and PANCR. The genomic deletion cosegregated with the major ARS symptoms observed in the family members. Conclusions: With the help of WES, qPCR, and long-range PCR, we identified a genomic deletion encompassing PITX2 and the adjacent noncoding gene PANCR in a Chinese family with ARS. The clinical features of the affected individuals are reported. This work may broaden understanding of the phenotypic and mutational spectrums related to ARS.

Utilisation of advanced MRI techniques to understand neurovascular complications of PHACE syndrome: a case of arterial stenosis and dissection.

PHACE syndrome is a rare disorder with posterior fossa brain malformations, segmental infantile haemangiomas, arterial anomalies, cardiac defects and eye anomalies. Cerebral and cervical arterial abnormalities occur commonly in these patients, predisposing subjects with PHACE syndrome to neurovascular complications including migraine-like headaches, moyamoya vasculopathy, arterial dissection and arterial ischaemia stroke. We leveraged institutional MRI protocols developed for adult neurovascular disease to better elucidate the pathogenesis of the arterial alternations observed in PHACE. Using high-resolution vessel wall and 4D flow MRI, we demonstrated enhancement, focal dissection and altered blood flow in a 7-year-old girl with PHACE syndrome. This is the first-time vessel wall imaging has been used to detail the known arterial changes in PHACE, and these findings may indicate that progressive vascular narrowing and vessel wall changes/inflammation are a factor in chronic headaches and other arterial complications seen in subjects with PHACE syndrome.

A variable presentation of Joubert syndrome: Case report and a brief review.

Joubert syndrome is a rare neurological manifestation usually present in late infancy or early childhood with characteristic episodes of abnormal breathing pattern along with the neurological and other systemic involvement.We report a case of confirmed Joubert syndrome present in the immediate neonatal period with isolated spells of oxygen desaturations not accompanied by the classically described breathing pattern and absent neurological symptoms causing delay in the diagnosis. Isolated oxygen desaturation episodes could be a presenting manifestation of Joubert syndrome in a neonatal period.

Electroretinographic Assessment in Joubert Syndrome: A Suggested Objective Method to Evaluate the Effectiveness of Future Targeted Treatment.

INTRODUCTION: Joubert syndrome (JS) is an autosomal recessive disorder characterized by a congenital malformation of the mid-hindbrain and a large spectrum of clinical features including congenital retinal dystrophy. The function of different retinal elements (rod, cone, bipolar cells) can be objectively evaluated by electroretinogram (ERG) recordings. Our work aims to evaluate the retinal function (by ERG recordings) in patients with JS with or without congenital retinal dystrophy. In addition, since clinical trials should be performed in the near future in JS, our results could provide information about the possible usefulness of ERG recordings in the assessment of the efficacy of treatments targeted to improve the retinal involvement. METHODS: In this observational and prospective study, 24 children with genetic identification for JS (mean age 10.75 ± 6.59 years) and 25 healthy age-similar normal control subjects (control group, mean age 10.55 ± 3.76 years) were enrolled. On the basis of the presence/absence of retinal dystrophy at fundus examination, patients with JS were divided into two groups: patients with JS with retinal dystrophy (16 children, mean age 11.00 ± 6.74 years, providing 16 eyes; JS-RD group) and patients with JS without retinal dystrophy (8 children, mean age 10.50 ± 6.45 years, providing 8 eyes; JS-NRD group). In patients with JS and controls, visual acuity (VA), dark-adapted, light-adapted, and 30-Hz flicker ERGs were performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. RESULTS: When compared to controls, patients in the JS-RD and JS-NRD groups showed significant abnormalities of the values of dark-adapted, light-adapted, and 30-Hz flicker ERG parameters. The ERG and VA changes were not significantly correlated. CONCLUSIONS: Our results suggest that a dysfunction of photoreceptors and bipolar cells occurs in patients with JS with or without retinal dystrophy. The retinal impairment can be detected by ERG recordings and this method should be proposed to evaluate the effectiveness of adequate treatment targeted to improve the retinal impairment in patients with JS.

Effect of peripapillary tilt direction and magnitude on central visual field defects in primary open-angle glaucoma with high myopia.

PURPOSE: To evaluate the relationship between peripapillary tilt and visual field (VF) defects in glaucomatous eyes with axial myopia. STUDY DESIGN: Retrospective cross-sectional study. PATIENTS AND METHODS: One hundred four eyes of 104 patients with primary open-angle glaucoma (POAG) with myopia were included (52 eyes with high myopia [HM], 26.5 mm ≤ axial length [AL] < 30.0 mm; and 52 eyes without HM, 24.0 mm < AL < 26.5 mm). The direction and magnitude of the peripapillary tilt were evaluated using optical coherence tomography. The eyes were divided into 12 groups according to the tilt directions defined by clock-hour sectors in a clockwise direction in the right eyes and in a counterclockwise direction in the left eyes. The mean deviation (MD) and central VF (CVF) values, ie, the mean threshold values of 4 paracentral points within 5 degrees of the Swedish Interactive Threshold Algorithm 30-2 test, were evaluated. RESULTS: The direction of the tilt was toward sector 9 (47.1%) and sector 8 (34.6%). The MD and CVF values were significantly worse (P = 0.013 and P = 0.019, respectively) in the sector 9 group than in the sector 8 group. Furthermore, the smaller peripapillary tilt magnitude in the sector 9 group was negatively correlated (P = 0.0019) with the CVF but not with the MD (P = 0.1) among the POAG eyes with HM. In contrast, the ovality index in the sector 9 group was not significantly correlated with the MD (P = 0.4) or the CVF (P = 0.36). CONCLUSION: A smaller temporal peripapillary tilt correlated with CVF defects in POAG eyes with HM. The peripapillary tilt direction and magnitude affect the CVF defect in POAG eyes with HM.