Outer Retinal Tubulation Research Articles

Geographic atrophy progression secondary to age-related macular degeneration: Five years of follow-up.

To study the progression of geographic atrophy (GA) secondary to age-related macular degeneration over a five-year follow-up. Eyes with GA included to assess demographic data, yearly optical coherence tomography (OCT) findings and the GA growth rate on infra-red (IR) images. A total of 41 eyes of 29 patients were included with a mean age of 81.76 ± 6.37 at baseline, and 65.51% were females. Over five years, there was a significant increase in the mean GA area from 8.44 ± 8.98 mm² to 13.32 ± 10.07 mm² (P < 0.001), with an annual growth rate of 1.14 ± 0.78 mm². The annual growth rates in females were slightly higher compared to males (1.29 ± 0.89 mm2 vs 0.96 ± 0.49 mm2, p = 0.569), and in smokers was slightly higher than non-smokers (1.35 ± 0.85 mm2 vs 0.94 ± 0.66 mm2, p = 0.100). Larger GA areas at the baseline showed higher GA progression in mm2 per year (P = 0.04). Smaller GA areas and fovea-spared GA at the baseline exhibited a larger percentage increase (P < 0.001 and P = 0.015, respectively). There was a lower GA progression rate in eyes with outer retinal tubulations (ORT) (P = 0.027), yet no significant correlation was found between GA progression and other OCT features. Smaller, fovea-sparing GA eyes experienced a more substantial proportional increase over five years. Also, The presence of ORT was associated with a slower rate of GA progression. Additionally, we observed a trend of faster GA growth in smokers and female genders.

Cross-Sectional Analysis of Outer Retinal Tubulation in Inherited Retinal Diseases: A Multicenter Study

PurposeThis study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene. DesignRetrospective cohort study. MethodsA retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient's respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across two gene-specific cohorts: non- retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes. ResultsAmong the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) forCHM, 100%(2/2) forPNPLA6, 100% (4/4) forRCBTB1, 100% formtDNA[100% (4/4) forMT-TL1and 100% (1/1) formtDNAdeletion], 100% (1/1) forOAT, 95.2% (20/21) forCYP4V2, 72.7% (8/11) forCHMfemale carriers, 66.7% (2/3) forC1QTNF5, 57.1% (8/14) forPROM1, 53.8% (7/13) forPRPH2, 42.9% (3/7) forCERKL, 28.6% (2/7) forCDHR1, 20% (1/5) forRPE65, 4% (18/445) forABCA4.In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such asRHO(n=13),USH2A(n=118),EYS(n=70),PDE6B(n=10),PDE6A(n=4),and others. ConclusionThese results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts.

Optical Coherence Tomography Characteristics for Differentiating Scars in Type 1 (Polypoidal Choroidal Vasculopathy (PCV)) and Type 2 (Classical) Macular Neovascularization (MNV) in Age-Related Macular Degeneration (AMD).

This study aimed to assess the optical coherence tomography (OCT) characteristics for differentiating scars in the scarred stages of macular neovascularization (MNV) in age-related macular degeneration (AMD). Medical records of 20 patients, 10 in each group with type 1 and type 2 MNV, were selected for the study. Participants chosen were above 50 years of age and underwent comprehensive eye examination alongside indocyanine green angiography (ICGA), fundus fluorescence angiography (FFA), and Spectralis optical coherence tomography (SOCT) (Heidelberg Engineering, Germany), respectively. The qualitative and quantitative OCT measurements, such as the frequency of outer retinal tubulations, presence of cystoid spaces, scar area, choroid thickness, retinal thickness, presence of disorganization in retinal layers (DRIL), foveal contour, and involvement of retinal layers in the scar, were meticulously evaluated and compared between the two groups. Significant disparities between type 1 MNV and type 2 MNV in choroidal thickness were identified in the nasal and superior quadrants within 1 mm, in the superior quadrant within 3 mm, and in all quadrants except the inferior quadrant within 6 mm. Overall, type 2 MNV showed thinner choroid than type 1 MNV. Although there are several overlapping features noticed between the groups, the OCT was able to pick up characteristic features that aid in differentiating type 1 (polypoidal choroidal vasculopathy (PCV)) and type 2 (classic) MNV in AMD. This precise differentiation has the potential to assist ophthalmologists in making well-informed decisions, thereby enhancing patient care.

Outer Retinal Tubulation in Geographic Atrophy.

Outer retinal tubulation (ORT) is observed on optical coherence tomography images from patients with geographic atrophy (GA), but its clinical implications are unclear. The objective of this study was to investigate the prevalence of ORT and its association with GA lesion growth rates. This post hoc longitudinal analysis assessed 62 eyes randomized to sham treatment in the phase 2 FILLY trial. ORT prevalence was estimated at baseline, month 12, and month 18 and change in GA lesion growth from baseline to month 18 was calculated. ORT prevalence rates were 24%, 43%, and 43% at baseline, month 12, and month 18, respectively. Slower mean GA lesion growth was observed in eyes with ORT present at baseline in the overall population as well as the subfoveal and nonsubfoveal GA subgroups. ORT presence may indicate a slower-growing GA lesion phenotype, independent of foveal involvement. [Ophthalmic Surg Lasers Imaging Retina 2024;55:448-451.].

Early Choriocapillaris Loss in a Porcine Model of RPE Cell Debridement Precedes Pathology That Simulates Advanced Macular Degeneration.

No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1month, 2months, 3months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2months (n = 3), 3months (n = 2), or 6months (n = 2) after surgery. RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point. Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.

Histologic and Immunohistochemical Characterization of GA-Like Pathology in the Rat Subretinal Sodium Iodate Model.

Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration with multifactorial etiology and no well-established treatment. A model recapitulating the hallmarks would serve as a key to understanding the underlying pathologic mechanisms better. In this report, we further characterized our previously reported subretinal sodium iodate model of GA. Retinal degeneration was induced in rats (6-8weeks old) by subretinal injections of NaIO3 as described previously. Animals were sacrificed at 3, 8 and 12weeks after injection and eyes were fixed or cryopreserved. Some choroids were processed as flatmounts while other eyes were cryopreserved, sectioned, and immunolabeled with a panel of antibodies. Finally, some eyes were prepared for transmission electron microscopic (TEM) analysis. NaIO3 subretinal injection resulted in a well-defined focal area of retinal pigment epithelium (RPE) degeneration surrounded by viable RPE. These atrophic lesions expanded over time. RPE morphologic changes at the border consisted of hypertrophy, multilayering, and the possible development of a migrating phenotype. Immunostaining of retinal sections demonstrated external limiting membrane descent, outer retinal tubulation (ORT), and extension of Müller cells toward RPE forming a glial membrane in the subretinal space of the atrophic area. TEM findings demonstrated RPE autophagy, cellular constituents of ORT, glial membranes, basal laminar deposits, and defects in Bruch's membrane. In this study, we showed pathologic features of a rodent model resembling human GA in a temporal order through histology, immunofluorescence, and TEM analysis and gained insights into the cellular and subcellular levels of the GA-like phenotypes. Despite its acute nature, the expansion of atrophy and the GA-like border in this rat model makes it ideal for studying disease progression and provides a treatment window to test potential therapeutics for GA.

OCT biomarkers in wet type age related macular degeneration

OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow‐up of AMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response.OCT biomarkers in wet type age related macular degeneration can be divided into two different categories.Biomarkers based on the retinal distribution of fluids and, structural biomarkers based on the presence or absence of specific features can be observed in the retinal layers, choroid, or vitreomacular interface.The aim of this review is to describe and analyse various structural OCT‐based biomarkers, which have practical value during both initial assessment and treatment follow‐up of wet type AMD patients.Central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management.The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid).In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analysed in detail.The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub‐RPE hyperreflective columns, pre‐choroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with AMD progression.This up‐to‐date review article provides a comprehensive description on how structural OCT‐based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in AMD patients.

Clinical Characteristics and Genetic Variants in Taiwanese Patients With PROM1-Related Inherited Retinal Disorders.

This study investigated the clinical characteristics of patients with PROM1-related inherited retinal diseases (IRDs). Patients diagnosed with IRDs who had mutations in PROM1 were identified at Linkou Chang Gung Memorial Hospital and Kaohsiung Medical University Hospital in Taiwan. Information on clinical characteristics and best-corrected visual acuity was recorded. Color fundus (CF) images, fundus autofluorescence photography (FAF), spectral-domain optical coherence tomography (SD-OCT), and electroretinograms (ERGs) were analyzed to examine patient phenotypes. PROM1 variants were detected using whole exome sequencing and verified by Sanger sequencing. Fourteen patients from nine families with PROM1-related IRDs were analyzed. Most patients exhibited chorioretinal atrophy in the macular area, with or without extramacular involvement on CF. Similarly, hypo-autofluorescence confined to the macular area, with or without extramacular involvement, was present for most patients on FAF. Furthermore, SD-OCT revealed outer retinal tubulations and focal or diffuse retinal thinning. ERGs showed variable findings, including maculopathy with normal ERG, subnormal cone response, and extinguished rod and cone responses. We detected five variants of the PROM1 gene, including c.139del, c.794del, c.1238T>A, c.2110C>T, and c.1117C>T. In this study, we evaluated 14 Taiwanese patients with five PROM1 variants. Additionally, incomplete penetrance of heterozygous PROM1 variants was observed. Furthermore, patients with autosomal dominant PROM1 variants had lesions in the macular area and the peripheral region of the retina. SD-OCT serves as a useful tool for early detection of PROM1-related IRDs, as it captures certain signs of such diseases.

Imaging Histology Correlations of Intraretinal Fluid in Neovascular Age-Related Macular Degeneration.

Fluid presence and dynamism is central to the diagnosis and management of neovascular age-related macular degeneration. On optical coherence tomography (OCT), some hyporeflective spaces arise through vascular permeability (exudation) and others arise through degeneration (transudation). Herein we determined whether the histological appearance of fluid manifested this heterogeneity. Two eyes of a White woman in her 90s with anti-vascular endothelial growth factor treated bilateral type 3 neovascularization secondary to age-related macular degeneration were osmicated, prepared for submicrometer epoxy resin sections, and correlated to eye-tracked spectral domain OCT. Examples of intraretinal tissue fluid were sought among similarly prepared donor eyes with fibrovascular scars, in a web-based age-related macular degeneration histopathology resource. Fluid stain intensity was quantified in reference to Bruch's membrane and the empty glass slide. Exudative fluid by OCT was slightly reflective and dynamically responded to anti-vascular endothelial growth factor. On histology, this fluid stained moderately, possessed a smooth and homogenous texture, and contained blood cells and fibrin. Nonexudative fluid in degenerative cysts and in outer retinal tubulation was minimally reflective on OCT and did not respond to anti-vascular endothelial growth factor. By histology, this fluid stained lightly, possessed a finely granular texture, and contained mainly tissue debris. Quantification supported the qualitative impressions of fluid stain density. Cells containing retinal pigment epithelium organelles localized to both fluid types. High-resolution histology of osmicated tissue can distinguish between exudative and nonexudative fluid, some of which is transudative. OCT and histological features of different fluid types can inform clinical decision-making and assist in the interpretation of newly available automated fluid detection algorithms.

Prevalence and optical coherence tomography analyses of outer retinal tubulations in Chinese population with inherited retinal diseases.

To investigate the prevalence of outer retinal tubulation (ORT) and its correlations with optical coherence tomography (OCT) parameters in Chinese population with inherited retinal diseases (IRDs). This retrospective study enrolled consecutive patients identified with IRDs and referred for genetic testing between February 2016 and April 2021. Clinical characteristics from medical records and features of cross-sectional B-scans were reviewed and analysed. The associations of patient-specific and ocular features with the presence of ORT were evaluated using univariate and multivariate analyses. Two hundred and three patients (401 eyes) with a mean age of 49.7 ± 16.7 years were enrolled. ORT was observed in 41 eyes (10.2%), including 26 of 28 eyes (92.9%) with Bietti crystalline corneoretinal dystrophy (BCD), 14 of 338 eyes (4.1%) with retinitis pigmentosa (RP), and 1 of 26 eyes (3.8%) in eyes with cone-rod dystrophy. Eyes with ORT showed significantly worse visual acuity than those without ORT (P = 0.002). Multivariate analysis indicated that the presence of ORT was positively correlated with choroidal atrophy and inner nuclear layer (INL) cysts (P < 0.01). ORTs were detected more frequently in eyes with BCD than RP (P = 0.024), most of which located exclusively within the extrafoveal area. Large choroidal vessels were detected underneath the corresponding ORTs in both patients with BCD and RP. The prevalence of ORT varies among different IRDs phenotypes, with the highest prevalence in BCD. The presence of choroidal atrophy and INL cysts may be associated with an increased risk of ORT formation in patients with IRD.

Characterization of peripheral blood inflammatory indicators and OCT imaging biological markers in diabetic retinopathy with or without nephropathy.

To observe the distribution characteristics of peripheral blood inflammatory indexes and retinal macular area optical coherence tomography (OCT) imaging biomarkers in patients with diabetic retinopathy (DR) with or without diabetic nephropathy (DN), in order to seek clinical biomarkers that can predict the development of DR and DN. A total of 169 inpatients with DR who visited the ophthalmology department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from October 2020 to June 2022 and had complete clinical data were collected, and the patients with DR were divided into two major groups, DR and DR/DN, according to whether they had DN, and then further divided into four subgroups, Non-proliferative DR(NPDR), proliferative DR(PDR), NPDR/DN and PDR/DN, according to the stage of DR. The distribution characteristics of peripheral blood inflammatory indexes [Neutrophil to lymphocyte ratio(NLR) and Platelet to neutrophil ratio(PLR)], renal function indexes [Cystatin-C(CYS-C), Creatinine(Crea), Uric acid(UA)and Urinary albumin to creatinine ratio(UACR)] and OCT imaging indexes [Hyperreflective foci(HRF), Disorgnization of retinal inner layers(DRIL), Outer retinal tubulations(ORTs), Central retinal thickness(CRT), Retinal nerve fiber layer(RNFL) and Ganglion cell layer(GCL)] were analyzed between the above subgroups. There was no difference between DR and DR/DN groups in terms of gender, family history of diabetes, duration of diabetes and Body mass index(BMI) (P>0.05), the mean age of the DR/DN group was significantly lower than that of the DR group (P<0.05), and the proportion of the DR/DN group with a history of hypertension was significantly higher than that of the DR group (P<0.05); there was no significant difference in hemoglobin A1C(HbA1c) between DR and DR/DN groups (P>0.05). (P>0.05), Hemoglobin(HGB) was significantly higher in the DR group than in the DR/DN group (P <0.05), NLR, PLR, Crea, UA and CYS-C were significantly higher in the DR/DN group than in the DR group (P<0.05); there was no significant difference in the comparison of HRF, DRIL, ORTs positive rate and CRT between the DR and DR/DN groups (P>0.05). RNFL and GCL thickness were significantly lower in the DR/DN group than in the DR group (P<0.05); history of hypertension (OR=2.759), NLR (OR=1.316), PLR (OR=1.009), Crea (OR=1.018), UA (OR=1.004), CYS-C (OR=3.742) were the independent (OR=0.951), age (OR=0.951), HGB (OR=0.976), RNFL (OR=0.909) and GCL (OR=0.945) were independent protective factors for DR/DN; RNFL (OR=0.899) and GCL (OR=0.935) were independent protective factors for NPDR/DN, RNFL (OR=0.852) and GCL (OR=0.928) were independent protective factors for PDR/DN. ROC curve analysis showed that the area under the curve (AUC) for CYS-C, PLR, Crea, UA and the combination of the four indicators to predict DR/DN were 0.717, 0.625, 0.647, 0.616 and 0.717, respectively. (1) Low age combined with hypertension HGB, NLR, PLR, CYS-C, Crea and UA may be serum biological markers for predicting DN in DR; meanwhile, PLR, CYS-C, Crea, UA and the combination of the four indicators can be used for risk assessment and adjunctive diagnosis of DN in DR combined with hypertension. (2) The RNFL and GCL thickness in the temporal aspect of the central macular sulcus may be imaging biological markers for predicting DN in DR; meanwhile, GCL thickness may have important value for risk prediction and diagnosis of DN in combination with DR.

Clinical and Genetic Findings in Korean Patients with Choroideremia.

We share and analyze the clinical presentations and genotypes of Korean male patients and female carriers who visited our clinic. Six male patients and three female carriers with comprehensive ophthalmic examinations and next-generation sequencing were included. Detailed clinical features were identified using visual field (VF) test and multimodal imaging including color fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT). Six male patients were diagnosed with choroideremia at the median age of 25 years. Before genetic testing, three (50.0%) patients were clinically diagnosed with choroideremia, while the other three (50.0%) patients with retinitis pigmentosa (RP). Patients showed different types of hemizygous CHM mutation, including two nonsense mutations (c.715C>T, p.Arg239Ter; c.799C>T, p.Arg267Ter), two frameshift mutations (c.1584_1587del, p.Val529HisfsTer7; c.403_404delGA, p.Asp135PhefsTer9), one splicing mutation (c.1511-28_1511-2del), and one exon duplication (2-9). The latter three mutations are novel findings. Two female carriers showed exon duplication (2-9) and the other one female carrier showed nonsense mutations (c.715C>T, p.Arg239Ter) in heterozygote form. Fundus showed diffuse yellow-whitish scleral reflex and granular pigmented lesions. FAF showed multiple patchy hypofluorescence lesions, sparing macula. OCT showed thinning of outer nuclear layer, ellipsoid zone, RPE layer, choroid thickness, interlaminar bridges (ILBs), outer retinal tubulations (ORTs), and microcysts in the inner nuclear layer. VF showed ring scotoma pattern with small amount of remaining central field. Asymptomatic female carriers showed variable fundus findings and mild changes in OCT. A detailed description of the genotypes with three novel mutations and phenotypes of six choroideremia patients and three CHM mutation female carriers are presented.

Pentosan polysulfate maculopathy: a brief primer for general practitioners, ophthalmologists, optometrists and urologists.

Pentosan polysulfate maculopathy: a brief primer for general practitioners, ophthalmologists, optometrists and urologists.

Outer retinal tubulation in Bietti crystalline dystrophy associated with the retinal pigment epithelium atrophy.

To determine the prognostic value of outer retinal tubulation (ORT) in the eyes of a Chinese cohort with Bietti crystalline dystrophy (BCD). This retrospective, multicenter cohort study enrolled forty-two patients with clinically and genetically diagnosed BCD. Eighty eyes with good-quality images of spectral domain optical coherence tomography (SD-OCT) were included. Demographic details and clinical data were collected. The characteristics of ORT, including prevalence, location and morphologic characteristics were analyzed. Forty-two BCD patients harbored potentially CYP4V2 disease-causing mutations. The mutation spectrum comprised 17 unique variants, nine of which were novel. Fifty-two of these 80 eyes demonstrated evidence of ORT. The incidence of ORT is significantly higher in stage 2 than other stages (P<0.001). ORT was mainly bilateral and located at margin of the atrophic area of retinal pigmental epithelial (RPE), and dynamically changed with the progressive RPE atrophy. The process of RPE atrophy was slower in eyes with ORT (P=0.017), with significantly longer intact RPE width in stage 3 (P=0.024). Eyes with ORT had slower vision loss than eyes without ORT (P=0.044). ORT may be a sign of the onset of RPE atrophy in early-stage BCD and may suggest less risk of rapid progression in late-stage BCD.

Presumed Bietti crystalline dystrophy with optic nerve head drusen: a case report

BackgroundBietti crystalline dystrophy is primarily a retinal dystrophy caused by a CYP4V2 mutation and typically presents with crystalline retinal deposits in the posterior fundus.Case presentationWe present the case of an otherwise healthy 39-year-old Iranian woman with no family history of ocular disease who suffered with progressive vision loss that had started 2 years prior to presentation. Ocular examination revealed blurry optic nerve head margin and diffuse retinal crystalline deposit in both eyes. Spectral domain optical coherence tomography images showed retinal crystals, located mostly in outer retinal layers, with some areas of outer retinal tubulation and attenuation of outer retinal layers. Crystalline deposits were better visualized on near-infrared images as hyperreflective spots. Fundus autofluorescence images showed hyperautofluorescence areas on optic nerve head consistent with optic nerve head drusen and large hypoautofluorescence areas in posterior retina consistent with retinal pigment epithelium atrophy. Cystinosis was ruled out by blood testing.ConclusionBietti crystalline dystrophy may be associated with optic nerve head drusen.

Structural and functional phenotypic features and molecular analysis of Indian patients with Bietti crystalline dystrophy.

Purpose:Bietti crystalline dystrophy (BCD) is a rare retinal dystrophy, uncommon in Indians. This study describes the various phenotypic features seen in the Indian population.Methods: In this retrospective, descriptive case series, records of patients with either clinical or molecular diagnosis of BCD from 2009 to 2020 were perused. Phenotypic and genotype information was collected and analyzed.Results: This study included 58 patients of BCD (31 males) aged 21–79 years (mean: 47 ± 14 years). The age at onset ranged from 7 to 41 years (mean: 28.8 ± 5.1 years). Vision ranged from 20/20 to counting fingers. There were 18 (31%) patients with stage 1 with crystals and mild retinochoroidal atrophy, 22 (38%) with stage 2 with atrophy extending beyond arcades, and 18 (31%) with absent crystals and extensive atrophy of stage 3. Choroidal neovascular membrane was seen in four patients. The optical coherence tomography showed retinochoroidal thinning (84.6%), outer retinal tubulations (71.8%), and paradoxical foveal thickening with interlaminar bridges (7.7%). Electrophysiology and visual fields showed reduced responses in advanced retinochoroidal changes. Molecular confirmation was available in five patients; five mutations were seen in the CYP4V2.Conclusion: A wide variation is seen in the phenotypic picture of BCD. A molecular diagnosis is helpful in differentiating from other retinal dystrophies. The OCT shows the peculiar feature of the interlaminar bridge in early cases with photoreceptor loss. Further investigations into this OCT feature may provide insights into the pathogenesis of BCD. A genotype–phenotype correlation could not be done.

Clinical and genetic findings in a Chinese cohort with choroideremia.

Choroideremia (CHM) is an X-linked chorioretinal dystrophy caused by variants in the CHM gene. The aim of this study was to report the clinical and genetic features of a cohort of affected males with CHM and establish the relationship between best correct visual acuity (BCVA) and age. Twenty-seven patients from 24 unrelated families underwent detailed ophthalmic examinations and comprehensive molecular genetic analysis. We combined the 27 patients in our own cohort with 68 Chinese patients from six previously reported studies to determine a transition age for BCVA rapid decline in 95 patients. Twenty-three causal (9 novel) CHM variants were identified in the 27 patients, who had a mean age of 30.5 ± 17.4 years and a mean BCVA (LogMAR) of 0.61 ± 0.79. Patients at different disease stages showed different extents of retinal pigment epithelium (RPE) and choroid abnormalities. Central retinal optical coherence tomography (OCT) scanning revealed defects in the ellipsoid zone and RPE in all patients and outer retinal tubulations in 75%. The 95 patients had a mean age of 33.27 ± 16.27 years and an average (LogMAR) of 0.72 ± 0.82. The BCVA did not decline rapidly before age 25, but decreased at a mean rate of 0.037logMAR/year after that age. Our results indicated Chinese patients with CHM variants have a younger transition age for rapid BCVA decline than previously reported for other ethnic groups. Central retinal OCT scanning can identify different abnormalities in the retinal structures, and these might be used as other parameters for monitoring disease progression in patients with CHM.

Morphologic and Microvascular Differences Between Macular Neovascularization With and Without Subretinal Fibrosis.

PurposeTo evaluate morphologic and microvascular differences between eyes with and without subretinal fibrosis (SF) caused by neovascular age-related macular degeneration (nAMD).MethodsPatients with nAMD with a minimum history of 12 months of anti-VEGF treatment were prospectively included in this cross-sectional study. Patients were imaged using standard imaging, swept-source optical coherence tomography angiography for quantitative microvascular analysis and polarization-sensitive OCT as an ancillary method for automated SF segmentation. The presence of reticular pseudodrusen, hyperreflective foci (HRF), and outer retinal tubulation (ORT) were also evaluated.ResultsSixty eyes of 60 participants (37 female) with nAMD and a mean 3.1 (±2.7)-year history of anti-VEGF treatment were included, 20 (33%) of which were diagnosed with SF. Eyes with SF had a higher prevalence of ORT (P < 0.001) and a lower prevalence of HRF (P = 0.004) than eyes without SF. Fifty eyes were analyzed quantitatively for microvascular biomarkers. Eyes with SF had a larger greatest vascular caliber (P = 0.001) and greatest linear diameter (P = 0.042), a larger microvascular neovascularization (MNV) area (P = 0.026), larger vessel area (P = 0.037), higher number of vessel junctions (P = 0.025), longer total vessel length (P = 0.027), higher number of vessel endpoints (P = 0.007), and higher endpoint density (P = 0.047).ConclusionsThis multimodal imaging approach demonstrated in vivo microvascular and morphological differences in eyes with and without SF. Eyes with SF tend to have larger MNV lesions with thicker vessels and are often associated with the presence of ORT.Translational RelevanceThis study points out imaging biomarkers in patients with SF, which may help identifying high-risk patients.

Complications, treatments, and visual prognosis of choroidal osteomas.

This study aims to report complications, treatments, and visual prognosis of choroidal osteoma. We retrospectively reviewed electronic medical records and multimodal images of 41 patients with choroidal osteoma. Visually significant complications included choroidal neovascularization (CNV) in 21 (47.7%) eyes and subretinal fluid (SRF) without CNV in 14 (31.8%) eyes. The most common treatment was intravitreal anti-vascular endothelial growth factor (VEGF) injection: 13 (61.9%) eyes with CNV received an average of 6.3 injections, and 6 (42.9%) eyes with SRF but without CNV received 1.8 injections. As the first-line treatment, intravitreal anti-VEGF injection induced complete or partial remission in 93.4% of eyes with CNV and 57.1% of eyes with SRF. The probability of legally low vision estimated at 3 and at 5years was 29.1% and 34.2%, respectively. The presence of CNV and outer retinal tubulation (ORT) was independent risk factors for vision loss (adjusted odds ratio, 8.08 and 6.94, respectively). The development of CNV and ORT was strong risk factors for visual impairment. Due to the frequent recurrence of complications and poor visual prognosis, regular check-ups and appropriate treatment choices are warranted.

Genotype and Ocular Phenotype in Sixteen Chinese Patients with Bietti Corneoretinal Crystalline Dystrophy

ABSTRACTObjectiveTo investigate CYP4V2 gene variants and ocular clinical characteristics of Bietti corneoretinal crystalline dystrophy in China so as to provide more references for genotype and phenotype of BCD.MethodsSixteen Chinese probands were recruited in Beijing Tongren Hospital in a retrospective study. All patients underwent CYP4V2 gene detection and ophthalmic clinical examinations.ResultsCYP4V2 gene variants were detected in all patients. Eight variants were identified, and the most common one was c.802–8_810del17bpinsGC. Onset age of BCD was from 12 to 44 years, and the first symptoms mostly were decreased visual acuity or night blindness. Corneal crystalline depositions were observed in all patients and were found not only in epithelium and superficial stroma near the limbus but also in corneal endothelium. OCT showed atrophy of RPE in all patients, outer retinal tubulation in ten patients, macular edema in four patients, macular hole in three patients with one accompanied with retinal detachment, and choroidal neovascularization in one patient.ConclusionCYP4V2 gene variants were detected in all patients consistent with the genetic locus homogeneity of BCD, and c.802–8_810del17bpinsGC was the most common mutation. Corneal crystalline depositions were observed in all patients, which may be features of BCD and helpful for the diagnosis of BCD patients, especially those in the advanced stage without typical fundus crystalline depositions or without gene detection. However, considerable phenotypic variability was detected. Corneal crystalline deposits were observed not only in epithelium and superficial stroma but also in endothelium, which has not been reported before. This may provide further evidence for the variable phenotypic expression between affected individuals.