Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens.

AIM: To investigate the clinical characteristics, treatment methods and outcomes of rhegmatogenous retinal detachment (RRD) in highly myopic eyes with implantable collamer lens (ICL). METHODS: High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed. Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient. RESULTS: A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included. The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo (range, 1-60mo). At the initial visit for RRD, giant retinal tear (GRT), horseshoe tear, simple round hole, and horseshoe tear combined with round hole were detected in 3, 3, 2, and 1 eye(s), respectively, with macula-off in eyes. Eight patients received surgical treatment, and one patient was treated by retinal laser photocoagulation alone. The ICL was preserved in 7 eyes. At the last follow-up, the mean best corrected visual acuity (BCVA) improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR (P=0.035), and no case of recurrent retinal detachment was found. CONCLUSION: The morphological presentation of retinal breaks is diverse in this study. The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data, companied with acceptable visual and anatomical outcomes.

TYR mutation in a Chinese population with oculocutaneous albinism: Molecular characteristics and ophthalmic manifestations.

Oculocutaneous albinism (OCA) is a rare inherited disorder characterized by a partial or complete reduction of melanin biosynthesis that leads to hypopigmentation in the skin, hair and eyes. The OCA1 subtype is caused by mutations in TYR. The purpose of this study was to investigate the genetic and clinical ophthalmic characteristics of TYR mutations in patients with OCA. Herein, 51 probands with a clinical diagnosis of OCA were enrolled. Whole-exome sequencing and comprehensive ophthalmic examinations were performed. Overall, TYR mutations were detected in 37.3% (19/51) in the patients with OCA. Fifteen patients had compound heterozygous variants, and four cases had homozygous variants. Eleven different pathogenic variants in TYR were detected in these 19 patients, with missense, insertion, delins and nonsense in 71.1% (27/38), 15.8% (6/38), 2.6% (1/38), and 10.5% (4/38), respectively. Clinical examinations revealed that 84.2% (16/19) of patients were OCA1A, and 15.8% (3/19) were OCA1B. Most TYR probands (52.6%, 10/19) had moderate vision impairment, 15.8% (3/19) had severe visual impairment, 10.5% (2/19) exhibited blindness, only 5.3% (1/19) had mild visual impairment and 15.8% (3/19) were not available. Photophobia and nystagmus were found in 100% (19/19) of the patients. In addition, grade 4 foveal hypoplasia was detected in 100% (12/12) of the patients. In conclusion: The TYR patients exhibited severe ocular phenotypes: the majority (93.8%, 15/16) of them had a moderate vision impairment or worse, and 100% (12/12) had severe grade 4 foveal hypoplasia. These novel findings could provide insight into the understanding of OCA.

Improvement in health-related quality of life with Botulinum toxin A injection in acquired superior oblique palsy.

Purpose: This study aimed to investigate the outcomes of Botulinum toxin A (BTA) injection into the inferior oblique (IO) muscle for the management of unilateral acute acquired superior oblique palsy (SOP) and to evaluate changes in health-related quality of life post-injection using the Adult Strabismus-20 (AS-20) questionnaire. Methods: A prospective cohort study was performed in patients with unilateral acute acquired SOP who received BTA injections. Four units of BTA were injected into the ipsilateral IO muscle. Ocular examinations were performed pre-and post-injection, including alignment, ocular movement, and cyclotorsion deviation. The patients' AS-20 questionnaire scores were analyzed. Results: A total of 21 patients with acute acquired SOP were included. The initial median vertical deviation was 5 PD (range 1-16), which was improved to 0 PD (range 0-10) at both 1 and 6 months post-injection (p < 0.001 and p < 0.001, respectively). The median torsional deviation was 7° (range 2-18) at baseline and resolved to 0 degrees (range -3-5) at the 1-month and 0° (range -2-7) at the 6-month follow-up (p < 0.001 and p < 0.001, respectively). There were significant increases in the overall score (OAS), psychosocial subscale score (PSS), and functional subscale score (FSS) from baseline values at both the 1-month (p < 0.001, p < 0.001, and p = 0.001, respectively) and 6-month follow-up (all p < 0.001). Conclusion: Injecting BTA into the ipsilateral IO muscle successfully resolved vertical and torsional deviations and significantly improved quality-of-life scores. Our findings show that BTA treatment, as an early treatment for acute acquired SOP, can help patients by significantly improving their quality of life.

Clinical Features and Novel Genetic Variants Associated with Hermansky-Pudlak Syndrome.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive syndromic form of albinism, characterized by oculocutaneous albinism (OCA) and other systemic complications. The purpose of this study was to investigate patients with HPS-associated gene mutations and describe associated ocular and extraocular phenotypes. Fifty-four probands clinically diagnosed as albinism were enrolled. Ophthalmic examinations and genetic testing were performed in all subjects. The phenotypic and genetic features were evaluated. HPS-associated gene mutation was identified in four of the patients with albinism phenotype. Clinically, photophobia, and nystagmus was detected in all (4/4) patients, and strabismus was found in one (1/4) patient. Fundus examination revealed fundus hypopigmentation and foveal hypoplasia in all (8/8) eyes. Eight novel causative mutations were detected in these four HPS probands. Five (62.5%, 5/8) of the mutations were nonsense, two of the mutations were missense (25%, 2/8), and one of the mutations was frameshift (12.5%, 1/8). All patients in our study carried compound heterozygous variants, and all these pathogenic variants were identified to be novel, with most (62.5%, 5/8) of the mutations being nonsense. Our results improved the understanding of clinical ocular features, and expanded the spectrum of known variants and the genetic background of HPS.

Reading speed in school-age children with intermittent exotropia.

Reading speed in intermittent exotropia (IXT) children has been minimally examined. This study assessed reading speed in school-age children with IXT and determined clinical characteristics of IXT that impacted their reading ability. We compared the reading speed of 63 school-age (10-14 years) children with IXT to 44 age-matched normal counterparts. In addition, the correlation between reading speed and clinical characteristics of IXT were evaluated. The reading speed in children with IXT was 231 ± 51 CPM, while reading speed in normal counterparts was 257 ± 33 CPM. Age, gender were found to be factors associated with reading speed in children with IXT. After adjusting for the age and gender, we found a significant correlation between the LogTNO and reading speed in IXT group based on a generalized linear model (p = 0.014). These data show that reading speed was slower in school-age children with IXT assessed with the International Reading Speed Texts. When age and gender were adjusted, poor stereo function at near was found to be related with a slower reading speed.

Novel Compound Heterozygous BBS2 and Homozygous MKKS Variants Detected in Chinese Families with Bardet-Biedl Syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare multisystem developmental disorder. In this study, we report the genetic causes and clinical manifestations in two Chinese families with BBS. MATERIALS AND METHODS: Two families were recruited in this study. Family A was a four-generation family with four affected and 15 unaffected members participating in the study, and family B was a consanguineous family with one affected and three unaffected members participating. Whole exome sequencing was performed in the two families, followed by a multistep bioinformatics analysis. Sanger sequencing was used to verify the variants and to perform a segregation analysis. Comprehensive ocular and systemic examinations were also conducted. RESULTS: Novel compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A (p.G250R) was detected in the MKKS gene in family B. Both families presented with retinitis pigmentosa; however, except for polydactyly, all other systemic manifestations were different. All of the affected family members in family A were overweight with a high body mass index (range from 26.5 to 41.9) and high blood pressure. Family A also presented with a delay in the onset of secondary sex characteristics and genital anomalies, while other systemic abnormalities were absent in family B. CONCLUSIONS: This study presents one family with two novel BBS2 variants, expanding the variant spectrum of BBS, and one family with a known homozygous MKKS variant. The different phenotypes seen between the families with BBS2 and MKKS variants will contribute to the literature and our overall understanding of BBS.

Ultra-wide-field scanning laser ophthalmoscopy and optical coherence tomography in FEVR: findings and its diagnostic ability.

BACKGROUND/AIMS: To describe some novel vitreoretinal microstructural findings in patients with mild familial exudative vitreoretinopathy (FEVR) on ultra-wide-field scanning laser ophthalmoscopy (UWF-SLO) and UWF optical coherence tomography (UWF-OCT) and to evaluate their clinical significance. METHODS: A total of 32 patients and 32 healthy controls were studied. An additional independent 40 FEVR patients, 44 patients with non-FEVR retinopathies and 40 healthy controls participated in a diagnostic test to validate the abilities of novel findings in FEVR screening. RESULTS: A novel anatomic change, named Temporal Mid-Peripheral Vitreoretinal Interface Abnormality (TEMPVIA), was found on UWF-SLO in 88.3% of FEVR patients and in none of the healthy controls. The clinical significance of TEMPVIA was further validated by a diagnostic test in new independent cases, with satisfying sensitivity (91.5%) and specificity (98.8%) and Youden Index 0.90. In addition to foveal hypoplasia, some previously unrecognised, novel clinical changes in FEVR, for instance, retinoschisis, focal retinal thickening, sudden thinning of the retina and retinal ridge, were identified using UWF-OCT. CONCLUSION: The results of this study have led to an update of the clinical spectrum of FEVR and have improved our understanding of its pathogenesis. TEMPVIA is therefore suggested to be a useful biomarker in the screening strategy for mild FEVR.

Clinical features of ocular toxocariasis: a comparison between ultra-wide-field and conventional camera imaging.

PURPOSE: The purpose of this study is to compare the lesion detection rates of ocular toxocariasis (OT) between ultra-wide-field scanning laser ophthalmoscopy (UWF-SLO) and conventional fundus photography (CFP), and to evaluate the potential diagnostic ability of UWF-SLO in OT. METHODS: A total of 56 patients with serological/immunological confirmed unilateral OT were enrolled. The presence of OT characteristic features included the posterior granuloma (postG), peripheral granuloma (periG), tractional retinal detachment (TRD), retinal folds (RF), and vitreous strands (VS) and was analyzed in 36 patients with UWF-SLO and 56 patients with CFP. Diagnostic tests were employed using the clinical examination as gold standard. RESULTS: In total of the 56 OT eyes, granulomas were identified in 91.1% (51/56) of eyes, including postG in 46.4% (26/56) of eyes, periG in 41.1% (23/56) of eyes, and combined granulomas in 3.6% (2/56) of eyes. TRD, RF, and VS were found in 28.6% (16/56), 51.8% (29/56), and 83.9% (47/56) of patients, respectively. Although the specificities of the diagnosis in clinical features were similar by the diagnostic tests, the sensitivities of postG, periG, TRD, RF, and VS using UWF-SLO were 100%, 100%, 66.7%, 95%, and 81.8%, respectively, which were significantly higher those of CFP (72.2%, 31.3%, 11.1%, 55%, and 48.5%). Additionally, the extent of vitreous haze was milder graded by UWF-SLO compared to CFP (p = 0.0099). CONCLUSIONS: The diagnostic ability of UWF-SLO was superior to CFP using clinical examination as gold standard for the ascertainment of the characteristic manifestations of OT, especially for granulomas and RF.

New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma.

BACKGROUND: Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. METHODS: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. RESULTS: Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. CONCLUSIONS: A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.

Mutation Spectrum and De Novo Mutation Analysis in Stickler Syndrome Patients with High Myopia or Retinal Detachment.

Stickler syndrome is a connective tissue disorder that affects multiple systems, including the visual system. Seven genes were reported to cause Stickler syndrome in patients with different phenotypes. In this study, we aimed to evaluate the mutation features of the phenotypes of high myopia and retinal detachment. Forty-two probands diagnosed with Stickler syndrome were included. Comprehensive ocular examinations were performed. A targeted gene panel test or whole exome sequencing was used to detect the mutations, and Sanger sequencing was conducted for verification and segregation analysis. Among the 42 probands, 32 (76%) presented with high myopia and 29 (69%), with retinal detachment. Pathogenic mutations were detected in 35 (83%) probands: 27 (64%) probands had COL2A1 mutations, and eight (19%) probands had COL11A1 mutations. Truncational mutations in COL2A1 were present in 21 (78%) probands. Missense mutations in COL2A1 were present in six probands, five of which presented with retinal detachment. De novo COL2A1 mutations were detected in 10 (37%) probands, with a mean paternal childbearing age of 29.64 ± 4.97 years old. The mutation features of probands with high myopia or retinal detachment showed that the probands had a high prevalence of COL2A1 mutations, truncational mutations, and de novo mutations.

Identification of Novel Copy Number Variations of VCAN Gene in Three Chinese Families with Wagner Disease.

The VCAN/versican gene encodes an important component of the extracellular matrix, the chondroitin sulfate proteoglycan 2 (CSPG2/versican). Heterozygous variants targeting exon 8 of VCAN have been shown to cause Wagner disease, a rare autosomal dominant non-syndromic vitreoretinopathy that induces retinal detachment, cataracts and permanent visual loss. In this study, we report on six patients from three unrelated families with Wagner disease in whom we identified three novel copy number variations of VCAN. Quantitative real-time polymerase chain reaction analysis identified deletions, including one exon-intron boundary of exon 8 or both exons 8 and 9, causing the haploinsufficiency of VCAN mRNAs.

Novel variants in familial exudative vitreoretinopathy patients with KIF11 mutations and the Genotype-Phenotype correlation.

Familial exudative vitreoretinopathy (FEVR) is an inherited disease characterized by abnormal development of retinal vasculature. KIF11 mutations were identified to be associated with FEVR in recent years. The purpose of this study was to investigate novel variants and describe associated ocular and extraocular phenotypes in FEVR patients with KIF11 mutations. Herein, 417 probands with clinical diagnosis of FEVR were enrolled. Genetic testing and ophthalmic examinations were performed in all subjects, and the genotype-phenotype correlation was analyzed. Overall, KIF11 mutation was identified in nine probands (9/417, 2.2%) among the patients with FEVR phenotype. There were six males and three females whose median age was six months (range: four months to six years old) at first visit. Among the detected mutations, five (55.6%) were frameshift, two (22.2%) were missense, one (11.1%) nonsense, and one (11.1%) splicing. Seven of these KIF11 mutations were detected as novel. Four (4/9, 44.4%) of the mutations were de novo. Clinical examinations showed that: four probands presented with bilateral falciform retinal fold; two with bilateral tractional retinal detachment; one was observed tractional retinal detachment in one eye and retinal fold in the other eye; one had falciform retinal fold in one eye and chorioretinal atrophy in the other eye; one exhibited rhegmatogenous retinal detachment in the left eye. Six of the probands were detected to have microcephaly. In conclusion: Most (5/9,55.6%) of the causative mutations were frameshift, and nearly half (4/9, 44.4%) of the mutations were de novo. Most (8/9, 88.9%) patients with KIF11 mutations showed typical ocular manifestations of severe FEVR. Majority (6/9, 66.7%) of the probands had a KIF11 mutation and were detected to have microcephaly. Seven of these harbored KIF11 mutations detected to be novel.

Developmental Changes in Retinal Microvasculature in Children: A Quantitative Analysis Using Optical Coherence Tomography Angiography.

PURPOSE: To quantify the macular microvasculature in healthy children of various ages by using optical coherence tomography angiography (OCTA). DESIGN: Prospective cross-sectional study. METHODS: A total of 333 normal children from 4 to 16 years old were included. OCTA was performed on a 3- × 3-mm area centered on the macular region. Vascular density, perfusion density, fovea avascular zone (FAZ) area, FAZ perimeter, and FAZ acircularity index (AI) were measured and adjusted for axial length. Differences were compared among various ages. RESULTS: Among the different age groups, both macular vascular density and perfusion density increased with age (P < .0001 and P = .0028, respectively). After adjustments were made for the spherical equivalent (SE) and axial length, macular vascular density was significantly associated with age (r = 0.183; P = .001) No factors were significantly correlated with the perfusion density after adjustment for the age, SE, or axial length. The FAZ area and FAZ perimeter did not change among groups of different ages. Nevertheless, the AI of FAZ in the 4.00-6.99-year-old group was smaller to that of the 13.00-15.99-year-old group (P = .03). Younger children had significantly higher rates of nonconsecutive vessels branched toward the macular center (P = .0002) and vascular loops contributing to irregular shapes of FAZ (P = .024). CONCLUSIONS: Macular vascular density and perfusion density continuously increase with age in children. Despite the fact that FAZ area and perimeter did not change, the microstructure of FAZ pruned and tended to form a smooth and regular avascular area during development.

Analysis of Etiologic Factors in Pediatric Rhegmatogenous Retinal Detachment With Genetic Testing.

PURPOSE: The purpose of this study was to investigate the etiology and clinical features of nontraumatic rhegmatogenous retinal detachment (RRD) in children. DESIGN: Consecutive, cross-sectional study. METHODS: In this study, 112 operative eyes of 102 patients ≤18 years of age with nontraumatic RRD were included. Comprehensive ophthalmic examinations were performed in all patients. Genetic testing was performed in 34 patients with hereditary congenital/developmental diseases. The etiology of RRD was analyzed. RESULTS: The average age was 12.2 ± 4.5 years (range, 1-18 years). The percentages of male and female patients were 74.5% (76/102) and 25.5% (26/102), respectively. The most common etiologic factors were congenital/developmental anomalies (51/102, 50%), followed by simple myopia (34/102, 33.3%) and previous intraocular surgery (6/102, 5.9%). More than half (31/51, 60.8%) of the patients with congenital/developmental anomalies had familial exudative vitreoretinopathy. Further analysis of the underlying etiologic factors based on age revealed that the most common etiology of RRD in patients ≤12 years of age was congenital/developmental anomalies (28/48, 58.3%); however, simple myopia was the major etiologic factor in patients >12 years of age (27/54, 50%). CONCLUSIONS: Congenital/developmental diseases were the most common etiologies of pediatric nontraumatic RRD in China. Familial exudative vitreoretinopathy accounted for most of the congenital/developmental anomalies.

The spectrum of genetic mutations in patients with asymptomatic mild familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a disease exhibits a wide range of clinical signs, ranging mild peripheral retinal vascular anomalies to severe retinal detachments. Individuals with mild FEVR are frequently asymptomatic with good visual function and are often undiagnosed. However, little is known about the genetic characters of the cohort. The purpose of this study was to investigate the clinical characteristics and genetic spectrum of in patients with asymptomatic mild FEVR. Herein, sixty-two patients (124 eyes) with asymptomatic mild FEVR were studied in a case series. Comprehensive ophthalmic examinations and genetic testing were performed in all patients. Clinical examinations showed that the avascular zone was seen in all 124 eyes and was the most common abnormality observed. Increased vessel branching and straightened peripheral vessel branches were found in 122 (98.4%) eyes. Late-phase angiographic posterior and peripheral leakage (LAPPEL) was observed in 80 (64.5%) eyes and V-shape degeneration was noted in 36 (29.0%) eyes. Other manifestations including extensive anastomoses, retinal ridges, and extraretinal neovascularization, which were detected in 30 (24.2%), 10 (8.1%) and 2 (1.6%) eyes respectively. Overall, pathogenic mutations were identified in 48.4% (30/62) of individuals with asymptomatic mild FEVR. Mutations in FZD4, LRP5, TSPAN12, and KIF11 were detected in 21.0% (13/62), 12.9% (8/62), 12.9% (8/62), and 1.6% (1/62) of our patients respectively. Ten novel mutations were found. In conclusion: Pathogenic mutations in the known FEVR-associated genes were detected in nearly half (48.4%) of the asymptomatic mild FEVR cohort. Among these mutations, FZD4 was predominant, appearing in 21.0% of all individuals. Patients with asymptomatic mild FEVR should receive timely examinations, lifelong monitoring, and some of them need preventive therapy and treatment. Additionally, we discovered 10 novel variants, which may enable a deeper understanding of this disease.

ASSESSING THE ACTIVITY OF MYOPIC CHOROIDAL NEOVASCULARIZATION: Comparison Between Optical Coherence Tomography Angiography and Dye Angiography.

PURPOSE: This study aims to suggest a novel strategy for assessing the activity of myopic choroidal neovascularization (mCNV) based on optical coherence tomography angiography (OCTA) and to compare it with traditional fundus fluorescein angiography as the gold standard. METHODS: Macular OCTA images were obtained using RTVue XR Avanti with AngioVue. Morphologic features of mCNV lesions were analyzed. Characteristics of OCTA in 41 eyes with active mCNV and 41 eyes with inactive mCNV were analyzed. Optical coherence tomography angiography parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using fundus fluorescein angiography as the reference. RESULTS: Of the total 108 patients, 82 had OCTA images with good quality which were included in this study. Several anatomical features of the CNV lesions, including overall appearance, branching with tiny vessels, presence of anastomoses/loops, and choroidal dark halo, were considered the possible parameters associated with mCNV activity. The intra- and interobserver agreements were substantial. To evaluate the CNV activity, sensitivity of overall appearance, tiny vascular branching, and presence of anastomoses or loops were 65.9%, 82.9%, and 73.2%, respectively, whereas the specificity was 87.8%, 90.2%, and 92.7%, respectively. However, the choroidal dark halo showed low specificity (46.3%) and failed in terms of evaluating the activity of mCNV. A novel comprehensive procedure integrating branching as a major parameter and overall appearance and presence of anastomoses/loops as minor parameters was developed to evaluate mCNV activity with sensitivity of 95.1% and specificity of 85.4%. CONCLUSION: In mCNV, the acquisition rate of clear OCTA images was 75.9%. A novel comprehensive diagnostic procedure combining mCNV appearance, vascular branching, and anastomoses/loops by OCTA may be a valuable strategy to evaluate neovascular activity in mCNV.

Clinical manifestation and genetic analysis in Chinese early onset X-linked retinoschisis.

BACKGROUND: X-linked retinoschisis (XLRS) is one type of retinal dystrophy leading to the schisis of the neural retina and causing reduced visual acuity. The study aimed to investigate the clinical manifestations and retinoschisin 1 (RS1) mutations in Chinese patients with early onset XLRS. METHODS: Thirty-eight probands with early onset XLRS were recruited, comprehensive ophthalmic examination was performed. A targeted gene panel was used to test the RS1 mutations. RESULTS: All probands had RS1 hemizygous mutations including 16 known and 14 novel mutations. The median onset age was 2 years old (range 0.1-6 years). Probands with onset age ≤1 years. had more complications (retinal detachment and vitreous hemorrhage, p < 0.001), more mutations outside the discoidin domain and more non-frameshift mutations than probands with onset age >1 years. Macular and peripheral involvement was present in 77.27% of probands, and inner and outer nuclear layer splitting were present in 53.57% of probands. Electroretinography showed an electronegative waveform. The relatively rare phenotypes of lamellar macular hole and macular hole were present in a unilateral eye in three probands. CONCLUSION: In conclusion, the early onset XLRS developed more severe complications which need close monitoring and clinical manifestations illustrated here may facilitate the early diagnosis of retinoschisis.

Symmetry of folds in FEVR: A genotype-phenotype correlation study.

Familial exudative vitreoretinopathy (FEVR) is a hereditary retinal vascular disorder. Among the various clinical phenotypes of this disease, retinal folds are the primary and typical feature of FEVR. However, little is known about the clinical characteristics, genetic spectrum, or potential phenotype-genotype correlation of retinal folds. Herein, we describe and analyze the clinical and genetic characteristics of retinal folds in FEVR. Eighty-nine patients with unilateral or bilateral retinal folds were included in this study. Clinical examinations showed that the retinal folds were bilateral in 37 patients (41.6%). Various retinal abnormalities were noted in the fellow eyes in the remaining 52 patients with unilateral folds. Most of the folds were located temporally (98.4%, 124/126), and were complete (97.6%, 123/126). 67.5% (60/89) probands were genetic confirmed FEVR. 25 novel pathogenic mutations (7 in FZD4, 7 in LRP5, 1 in NDP, 4 in TSPAN12, and 6 in KIF11) were identified in 25 families. Overall, 87.5% (14/16) and 73.7%(14/19) patients with LRP5 and FZD4 mutations were with unilateral folds, respectively.Nevertheless, only 25% (2/8), 36.4%(4/11) and 16.7%(1/6) patients with NDP, TSPAN12, and KIF11 mutations were with unilateral folds. Moreover, 85.7%(12/14),100% (6/6) and 100%(8/8) of the patients with mutated TSPAN12, KIF11, and NDP genes presented with symmetry in disease staging, while 55% and 64.7% of patients with FZD4 and LRP5 mutation displayed symmetry in staging. In conclusion, the majority of retinal folds extended completely and radially in the temporal peripheral retina. Patients with causative mutations in NDP, TSPAN12, or KIF11 were more likely to have bilaterally symmetrical severe retinopathy. In contrast, patients with LRP5 and FZD4 mutations displayed a relatively milder but broader spectrum of phenotypes and a higher frequency of asymmetry.

Next-Generation Sequencing in the Familial Exudative Vitreoretinopathy-Associated Rhegmatogenous Retinal Detachment.

Purpose: The purpose of this study was to investigate the genetic mutation spectrum in Chinese patients with familial exudative vitreoretinopathy-associated rhegmatogenous retinal detachment (FEVR-RRD) and to analyze the preliminary genotype-phenotype association. Methods: In this consecutive, cross-sectional study, 54 patients with FEVR-RRD were studied. Comprehensive ophthalmic examinations and targeted next-generation sequencing were performed in all patients. The genotype-phenotype association was also analyzed. Results: Causative mutations were identified in 38.9% (21/54) of patients (14/54 in LRP5, 4/54 in FDZ4, and 3/54 in TSPAN12). The study identified 22 potentially pathogenic mutations in 21 unrelated FEVR probands, and 14 were novel (10/15 in LRP5, 1/4 in FZD4, and 3/3 in TSPAN12). Furthermore, to explore the genotype-phenotype association, late-phase angiographic posterior and peripheral leakage (LAPPEL) was identified in 100% (4/4) of patients with FZD4 mutations and 100% (3/3) of patients with TSPAN12 mutations but only in 42.9% (6/14) of patients with LRP5 mutations. Extraretinal neovascularization (ERNV) was found in 100% (4/4) of patients with FZD4 mutations and in 66.7% (2/3) of patients with TSPAN12 mutations, but only in 21.4% (3/14) of patients with LRP5 mutations. Conclusions: The positive rate for pathogenic mutations in the known FEVR-associated genes was 38.9% (21/54). Among the mutations, LRP5 mutation was the predominant, accounting for 66.7% (14/21) of genetic positive patients. Patients with FEVR-RRD due to LRP5 mutations have less retinal vascular leakage or neovasculization than do patients with FEVR-RRD due to TSPAN12/FZD4 mutations. Moreover, 14 novel variants were found, which provided a deeper understanding of this disease.

Novel ocular findings in oculodentodigital dysplasia (ODDD): a case report and literature review.

BACKGROUND: Oculodentodigitaldysplasia (ODDD; MIM no. 164200) is a rare hereditary disorder caused by mutations in the gene GJA1.Ocular disorders included microcornea, cornea opacity and glaucoma. However, few studies described fundus findings. MATERIALS AND METHODS: Ophthalmic examination included visual acuity measurement, intraocular pressure (IOP) measurements, slit-lamp biomicroscopy, B-scan ultrasonography, Ultrasound biomicroscopy (UBM), spectral-domain optical coherence tomography (SD-OCT), ERG and retcam fluorescein angiogram. In addition, blood samples were taken from this patient for mutation analyze of GJA1. RESULT: The ophthalmic features of this patient were microcornea, cornea opacity, glaucoma as expected. Interestingly, the patient had a normal axial length with refractive status of emmetropia, but extremely retinal dysplasia and severe choroid thinning was noted. Flash electroretinogram (ERG) was extinguished in both eyes. This study identified a novel mutation c.91A>T in the GJA1 gene associated with fundus abnormalities. Bioinformatics and structural modeling suggested the mutation to be pathogenic. CONCLUSION: Our research expanded not only the mutation spectrum, but also the clinical characteristics of ODDD. To the best of our knowledge, this is the first report on anatomical and functional chorioretinal changes in ODDD patients. These novel ocular features highlight the importance of fundus morphological and functional evaluation in ODDD. ABBREVIATIONS: ODDD: oculodentodigital dysplasia; OCT: optical coherence tomography; ERG: electroretinogram; TACT: teller acuity card test; UBM: ultrasound biomicroscopy; MW: molecular weights; AL: axial length; Cx43: connexin 43; RPE: retinal pigment epithelium; RGCs: retinal ganglion cells; FEVR: familial exudative vitreoretinopathy; ROP: retinopathy of prematurity.