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Frontiers in Medicine 2023X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, . Affected individuals develop retinal...
INTRODUCTION
X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, . Affected individuals develop retinal layer separation, leading to loss of visual acuity (VA). Several XLRS gene therapy trials have been attempted but none have met their primary endpoints. An improved understanding of XLRS natural history and clinical outcomes may better inform future trials. Here, we report the long-term functional and structural outcomes of XLRS and the relevance of genotypes to the visual prognosis of affected individuals.
METHODS
A retrospective chart review of patients with molecularly confirmed X-linked retinoschisis was performed. Functional and structural outcomes, and RS1 genotype data, were included for analysis.
RESULTS
Fifty-two patients with XLRS from 33 families were included in the study. Median age at symptom onset was 5 years (range 0-49) and median follow-up was 5.7 years (range 0.1-56.8). Macular retinoschisis occurred in 103 of 104 eyes (99.0%), while peripheral retinoschisis occurred in 48 of 104 eyes (46.2%), most often in the inferotemporal quadrant (40.4%). Initial and final VA were similar (logMAR 0.498 vs. 0.521; = 0.203). Fifty of 54 eyes (92.6%) developed detectable outer retinal loss by age 20, and 29 of 66 eyes (43.9%) had focal or diffuse outer retinal atrophy (ORA) by age 40. ORA but not central subfield thickness (CST) was associated with reduced VA. Inter-eye correlation was modest for VA (-squared = 0.03; = 0.08) and CST (-squared = 0.15; = 0.001). Carbonic anhydrase inhibitors (CAIs) improved CST ( = 0.026), but not VA ( = 0.380). Eight of 104 eyes (7.7%) had XLRS-related retinal detachment (RD), which was associated with poorer outcomes compared to eyes without RD (median final VA 0.875 vs. 0.487; <0.0001). null genotypes had greater odds of at least moderate visual impairment at final follow-up (OR 7.81; 95% CI 2.17, 28.10; = 0.002) which was independent of age at onset, initial CST, initial ORA, or previous RD.
DISCUSSION
Overall, long-term follow-up of XLRS patients demonstrated relatively stable VA, with presenting CST, development of ORA, and null mutations associated with poorer long-term visual outcomes, indicating a clinically relevant genotype-phenotype correlation in XLRS.
PubMed: 37396901
DOI: 10.3389/fmed.2023.1204095 -
Indian Journal of Ophthalmology Jan 2020
Topics: Adult; Eye Proteins; Humans; Male; Retina; Retinoschisis; Tomography, Optical Coherence
PubMed: 31856528
DOI: 10.4103/ijo.IJO_1521_19 -
Developments in Ophthalmology 2021Intraoperative portable handheld and microscope-integrated OCT enhance the pediatric vitreoretinal surgeon's diagnostic abilities during examination under anesthesia and... (Review)
Review
Intraoperative portable handheld and microscope-integrated OCT enhance the pediatric vitreoretinal surgeon's diagnostic abilities during examination under anesthesia and surgery, particularly in children who are challenging to examine preoperatively due to young age or ocular trauma. Improved OCT-guided visualization of vitreoretinal anatomic relationships has the potential to improve surgical safety and efficiency. In retinopathy of prematurity and other pediatric retinal vascular conditions, intraoperative OCT can be critical for distinguishing between retinoschisis and retinal detachment and highlighting abnormalities of the vitreoretinal interface that may contribute to development of tractional retinal detachments. During retinal detachment repair, intraoperative OCT aids identification of subtle retinal breaks, residual subretinal fluid, retained perfluorocarbon, preretinal membranes, and residual hyaloid, among other findings. In macular surgery, intraoperative OCT has demonstrated value in confirming completion or lack thereof of epiretinal and internal limiting membrane peeling and differentiating between lamellar and full-thickness macular holes. OCT-guided subretinal bleb formation and genetic vector delivery are critical to ensuring accurate localization of subretinal gene delivery for inherited retinal degenerations. Research on development of OCT-compatible surgical instruments, real-time three-dimensional volumetric OCT imaging, and integration with intraoperative OCT angiography are anticipated to further increase the utility of intraoperative OCT in pediatric vitreoretinal surgical decision-making.
Topics: Child; Humans; Retina; Retinal Diseases; Surgery, Computer-Assisted; Tomography, Optical Coherence; Vitreoretinal Surgery
PubMed: 33647898
DOI: 10.1159/000511818 -
Ophthalmic Genetics Oct 2023An 18-year old highly myopic woman presented with bilateral retinoschisis associated with a unilateral macular hole in the right eye and vitreomacular traction in the...
INTRODUCTION
An 18-year old highly myopic woman presented with bilateral retinoschisis associated with a unilateral macular hole in the right eye and vitreomacular traction in the left eye.
METHODS
Genetic studies disclosed a heterozygous pathogenic variant in the KCNJ13 gene was identified (c.484C>T (p.Arg162Trp)), consistent with a diagnosis of snowflake vitreoretinal degeneration (SVD).
RESULTS
While there were no corneal guttata, juvenile cataracts, or perivascular sheathing in this case, salient features of SVD included a fibrillar vitreous structure, crystalline retinopathy, and flattened optic nerves. The patient developed a FTMH in the left eye at 17 months follow up, followed by a rhegmatogenous retinal detachment (RRD) requiring 2 surgical repairs.
CONCLUSION
This case expands on the spectrum of clinical features in SVD, including retinoschisis and FTMH. It also characterizes optical coherence tomography findings in this rare disease entity. We emphasize the importance of using panel-based genetic testing to clinically distinguish and further define atypical vitreoretinopathies.
Topics: Female; Humans; Adolescent; Retinoschisis; Vitreous Body; Retinal Degeneration; Retinal Detachment; Retinal Perforations; Tomography, Optical Coherence
PubMed: 36440807
DOI: 10.1080/13816810.2022.2149816 -
Translational Vision Science &... Jun 2022The purpose of this study was to investigate the clinical characteristics of paravascular abnormalities (PVAs) and retinoschisis, and their associations with choroidal...
PURPOSE
The purpose of this study was to investigate the clinical characteristics of paravascular abnormalities (PVAs) and retinoschisis, and their associations with choroidal thickness (ChT) in young highly myopic (HM) adults.
METHODS
A total number of 645 eyes were included. Paravascular microfolds (PMs), paravascular cystoid spaces (PCs), paravascular lamellar holes (PLHs), and retinoschisis were detected using swept-source optical coherence tomography. Their associations with macular ChT and risk factors were analyzed.
RESULTS
PMs, PCs, and PLHs were detected in 203 (31.5%), 141 (21.9%), and 30 (4.7%) eyes, respectively. Retinoschisis was found in 50 (7.8%) eyes, 43 (86.0%) of which were located around the retinal vessels surrounding the optic disc. A decreasing trend of macular ChT (P < 0.001) was observed in the eyes with PMs only, with both PCs and PMs, and with PLHs, PCs, and PMs. After adjustments for age, sex, and axial length (AL), the presence of PCs, PLHs, or retinoschisis around the optic disc was negatively associated with macular ChT (all P < 0.05). Eyes with longer AL, incomplete posterior vitreous detachment (PVD), and myopic atrophic maculopathy (MAM) were more likely to have PCs (all P < 0.01) and retinoschisis around the optic disc (all P < 0.05).
CONCLUSIONS
PVAs were observed in approximately one third of the young HM adults in this study. The presence of PCs, PLHs, or retinoschisis around the optic disc was associated with thinner macular ChT. Eyes with longer AL, incomplete PVD, and MAM may be at risk of developing PVAs and retinoschisis around the optic disc.
TRANSLATIONAL RELEVANCE
PCs, PLHs, and retinoschisis around the optic disc could serve as early indicators for myopia progression.
Topics: Adult; Choroid; Humans; Myopia, Degenerative; Retinal Vessels; Retinoschisis; Tomography, Optical Coherence; Vitreous Detachment
PubMed: 35727187
DOI: 10.1167/tvst.11.6.18 -
Retinal Cases & Brief Reports Nov 2023To present two cases of concomitant retinal neovascularization (RNV) in acquired peripheral retinoschisis and analyze its characteristics on optical coherence tomography... (Review)
Review
PURPOSE
To present two cases of concomitant retinal neovascularization (RNV) in acquired peripheral retinoschisis and analyze its characteristics on optical coherence tomography angiography and based on a literature review.
METHODS
This was an observational, retrospective case study.
RESULTS
Case 1 presented with bullous retinoschisis and RNV near the schisis cavity. Optical coherence tomography angiography revealed no angioflow into the retinal arterioles of the cavity. An arterial filling delay to the retinoschisis with extensive leakage from the RNV was noted on fluorescein angiography. Case 2 involved the superficial retinoschisis and telangiectatic vessels inside the schisis cavity. Optical coherence tomography angiography revealed damage to the superficial capillary plexus of the cavity, absence of angioflow to the inner schisis layer, and increased angioflow to the RNV. Fluorescein angiography showed focal leakage from the RNV and diffuse leakage from telangiectasia. No vision-threatening complications were identified in either patient up to the last follow-up, subsequent to laser photocoagulation.
CONCLUSION
Acquired peripheral retinoschisis is associated with RNV. Inner retinal ischemia caused by hemodynamic resistance or a damaged superficial capillary plexus can interrupt angioflow to the inner schisis retinal layer on optical coherence tomography angiographic findings and develop RNV inside or outside the retinoschisis.
Topics: Humans; Retinoschisis; Retinal Neovascularization; Tomography, Optical Coherence; Retrospective Studies; Retinal Diseases; Fluorescein Angiography; Ischemia
PubMed: 35594561
DOI: 10.1097/ICB.0000000000001292 -
Experimental Eye Research Jan 2023PITX2 and FOXC1 are the most common pathogenic genes associated with Axenfeld-Rieger syndrome (ARS). In this study, we aimed to explore the variation spectrum of PITX2... (Review)
Review
PITX2 and FOXC1 are the most common pathogenic genes associated with Axenfeld-Rieger syndrome (ARS). In this study, we aimed to explore the variation spectrum of PITX2 and FOXC1 and their associated phenotype based on data from our study and previously reported literatures. Whole exome sequencing was performed on eight probands in our study. Multistep bioinformatic and co-segregation analyses were performed to detect pathogenic variants. Genotype-phenotype correlations of PITX2 and FOXC1 and the differences between them were determined. We detected three variants of FOXC1 and two variants of PITX2 in five unrelated families with ARS. Macular retinoschisis had been observed in AR1 with variant in PITX2 and it is not reported before. Additionally, a review of published literature and our study led to the identification of 593 families with variants of PITX2 or FOXC1, including 316 families with heterozygous variants in FOXC1, 251 families with heterozygous variants in PITX2, 13 families with variants in double genes, seven families with homozygous or compound heterozygous variants in FOXC1, and six families with variants in ADAMTS17, PRDM5, COL4A1 or CYP1B1. Significant differences were observed between the prevalence of missense and in-frame, truncation, and large deletion variants in PITX2 (32.00%, 42.67%, and 25.33%, respectively) and FOXC1 (34.49%, 35.13%, 30.38%, respectively) (p = 1.16E-43). Enrichment and frequency analyses revealed that missense variants were concentrated in the forkhead domain of FOXC1 (76.14%) and homeodomain of PITX2 (87.50%). The percentage of Caucasians with variants in FOXC1 was significantly higher than that of PITX2 (p = 2.00E-2). Significant differences between PITX2 and FOXC1 were observed in glaucoma (p = 3.00E-2), corectopia (p = 3.050E-6), and polycoria (p = 5.21E-08). Additionally, we observed a significant difference in best-corrected visual acuity (BCVA) between FOXC1 and PITX2 (p = 3.80E-2). Among all the family members with PITX2 or FOXC1 variants, the prevalence of systemic abnormalities was significantly higher in PITX2 than in FOXC1 (89.16% vs. 58.77%, p = 5.44E-17). In conclusion, macular retinoschisis as a novel phenotype had been observed in patient with variant in PITX2. Significant differences were detected in phenotypes and genotypes between PITX2 and FOXC1.
Topics: Humans; Anterior Eye Segment; Eye Abnormalities; Eye Diseases, Hereditary; Forkhead Transcription Factors; Genetic Association Studies; Homeodomain Proteins; Mutation; Pedigree; Retinoschisis; Homeobox Protein PITX2
PubMed: 36442680
DOI: 10.1016/j.exer.2022.109307 -
Clinical Ophthalmology (Auckland, N.Z.) 2020Pathologic myopia (PM) is an ocular disorder characterized by a spherical equivalent (SE) of more than - 6.0 diopters (D) or by an axial length (AL) of more than 26.5... (Review)
Review
Pathologic myopia (PM) is an ocular disorder characterized by a spherical equivalent (SE) of more than - 6.0 diopters (D) or by an axial length (AL) of more than 26.5 millimeters (mm). PM is associated with myopic maculopathy (MM). The ATN classification describes all the aspects of MM which regroups atrophic, tractional and neovascular consequences to the sclera, choroid and retina of highly myopic eyes. The advent of OCT allowed to define the ultrastructural characteristics of the tractional changes in MM, described by the term myopic traction maculopathy (MTM). They include foveoschisis/maculoschisis/retinoschisis (FS/MS/RS), retinal/foveal detachment (RD/FD), lamellar macular holes (LMH) and full-thickness macular holes (FTMH) with or without RD (MHRD). The MTM staging system (MSS) describes all foveal and retinal changes related to MTM and their natural history interpreting them as different stages of a single progressive disorder. The management of MTM can be just observation for the earliest cases with good vision or surgery for the severe stages with vision loss. There are two possible surgical approaches: ab externo, that acts on the alteration of the scleral shape and includes posterior scleral reinforcement and macular buckle. Ab interno, that targets the alteration of the foveal profile and consists in pars plana vitrectomy with removal of all the epiretinal tractions, maneuvers on the internal limiting membrane, and the use of intravitreal tamponade and laser. As they target two different sides of the same pathology, the two techniques have to be selected on the base of the MTM stage, single or combined.
PubMed: 33173268
DOI: 10.2147/OPTH.S237483 -
American Journal of Ophthalmology Case... Jun 2022To determine whether the Mizuo-Nakamura phenomenon, which is an important diagnostic sign of Oguchi's disease, also occurs in patients with genetically proven X-linked...
PURPOSE
To determine whether the Mizuo-Nakamura phenomenon, which is an important diagnostic sign of Oguchi's disease, also occurs in patients with genetically proven X-linked retinoschisis (XLRS).
METHODS
We examined three patients with a clinical and genetic diagnosis of XLRS and one patient who was clinically diagnosed with Oguchi's disease, with an emphasis on the Mizuo-Nakamura phenomenon. We obtained color fundus photographs, especially in the fully dark-adapted state, using the non-mydriatic mode on a digital retinal camera and infrared observation monitor to avoid the bleaching effects caused by the viewing light, which alters the fundus color in a short time.
RESULTS
The Mizuo-Nakamura phenomenon was observed in all patients with molecularly proven XLRS, similar to that in the patient with Oguchi's disease. The sets of photographs were obtained in the light- and dark-adapted states using our newly devised techniques needed to witness the Mizuo-Nakamura phenomenon.
CONCLUSIONS AND IMPORTANCE
The Mizuo-Nakamura phenomenon was identified in three patients with genetically proven XLRS. To the best of our knowledge, this study provided the first genetic evidence of the Mizuo-Nakamura phenomenon in a patient with molecularly proven XLRS without the causative genetic abnormalities for Oguchi's disease. Our findings suggest that XLRS is responsible for the Mizuo-Nakamura phenomenon and its presence in XLRS is not a rare exception but may be a consistent manifestation of XLRS.
PubMed: 35479517
DOI: 10.1016/j.ajoc.2022.101529 -
Investigative Ophthalmology & Visual... Aug 2022To evaluate spatial and temporal integration across the visual field in individuals with juvenile X-linked retinoschisis (XLRS).
PURPOSE
To evaluate spatial and temporal integration across the visual field in individuals with juvenile X-linked retinoschisis (XLRS).
METHODS
Nine subjects with XLRS and 10 visually normal individuals participated. Luminance thresholds were measured at 15 locations along the horizontal visual field meridian. Locations were grouped into four regions for analysis: foveal, parafoveal (2°), perifoveal (5°-10°), and peripheral (10°-60°). For spatial integration measurements, stimulus duration was 100 ms, and size ranged from 0.01 to 2.32 deg2 (Goldmann I-V). For temporal integration measurements, stimulus size was 0.15 deg2 (Goldmann III), and duration ranged from 12 to 800 ms. The effect of stimulus size and duration on the subjects' threshold was described using integration models.
RESULTS
Luminance thresholds for the XLRS group were more elevated for small targets (2.0×-12.6×) than for large targets (1.25×-3.2×) compared to controls for all locations. Likewise, thresholds for the XLRS group were more elevated for short durations (6.3×) than for long durations (4.0×) in the fovea and parafovea but were similarly elevated at all durations (2.0×-2.5×) in the perifovea and periphery. For both the size and duration experiments, thresholds measured in the fovea, parafovea, and perifovea of XLRS subjects were highly similar to those measured from the peripheral field of the controls.
CONCLUSIONS
Spatial and temporal integration characteristics of the XLRS fovea, parafovea, and perifovea are similar to those of the normal periphery. The results also indicate that scaling stimulus size equates thresholds for the XLRS and control subjects throughout the visual field, but scaling duration does not.
Topics: Fovea Centralis; Humans; Retinoschisis; Visual Fields
PubMed: 35984651
DOI: 10.1167/iovs.63.9.22