Dense Deposits Research Articles

Diagnostic and therapeutic challenges in dense deposit disease: case report

Diagnostic and therapeutic challenges in dense deposit disease: case report

A Case of Membranous Nephropathy Associated with Syphilis: Correlative Light and Electron Microscopy Revealing the Localization of Neuron-derived Neurotrophic Factor within Subepithelial Electron Dense Deposits.

A 50-year-old man presented to our hospital with a fever, edema, and a rash. The clinical diagnosis was renal dysfunction, nephrotic syndrome, and syphilis. The patient was treated with benzylpenicillin, and his symptoms improved. A renal biopsy revealed membranous nephropathy (MN). Recently, neuron-derived neurotrophic factor (NDNF) was reported to be an antigen corresponding to syphilis-associated MN. In the present patient, immunofluorescence staining and immunoelectron microscopy revealed granular NDNF-positive findings within subepithelial deposits, suggesting the presence of NDNF-IgG immune complexes. Although the mechanism by which NDNF serves as a target antigen remains unclear, NDNF was found to colocalize within subepithelial immune complexes in syphilis-associated MN.

Favorable outcome in children with dense deposit disease with the use of long-term mycophenolate mofetil and high-dose alternate-day steroids.

This study aimed to evaluate the response to therapy and outcome with long-term daily mycophenolate mofetil (MMF) and high-dose alternate-day steroids (HADS) in children with dense deposit disease (DDD). Children with DDD who received long-term MMF (1200mg/m2/day) and HADS (1.5-2mg/kg AD) with slow tapering were retrospectively evaluated for their clinico-pathological presentation, response to therapy (complete, partial, no remission) and outcome (patient and renal survival). Six out of eight children with DDD seen over 10years (3 boys, 3 girls) aged 6-13years received the above therapy. Clinical presentation was nephrotic syndrome (1/6), gross hematuria (2/6), and nephritic onset of nephrotic syndrome (3/6). Serum creatinine was elevated at presentation in 3/6; C3 levels were low in all. None had crescentic changes on biopsy. The duration of therapy was 2-3years. On therapy, haematuria resolved by 3months, and proteinuria decreased to non-nephrotic range by 12 to 18months in all six. Serum creatinine normalized, and all showed complete remission during treatment. Three had sustained remission. Two children relapsed while tapering steroids and attained partial remission on increasing the steroid dose. One patient relapsed, 1year after therapy completion and did not respond to restarting the same treatment. Over a mean follow-up period of 5years, patient and renal survival was 100%. Long-term treatment with MMF and HADS showed a beneficial effect in the resolution of proteinuria with preservation of renal function and survival in the medium term in children with DDD with nephritic/nephrotic presentation.

Very Late Recurrence of Dense Deposit Disease after Kidney Transplantation

A woman in her 40s with kidney failure secondary to biopsy-proven dense deposit disease (DDD) with positive C3 nephritic factor (C3Nef) and no complement gene defect received a kidney transplant from a deceased donor. Eighteen years after transplantation, laboratory workup revealed new-onset microscopic hematuria, with 547 red blood cells/μL (normal <25), and proteinuria, with a urine protein-to-creatinine ratio of 1.0 g/g creatinine (normal <0.150), increasing to 7.5 g/g within a few months. Glomerular filtration rate, estimated from the CKD-EPI equation, was normal (88 mL/min/1.73m2). Serum C3 level was very low (0.09 g/L, N 0.90 -1.80), while serum C4 level was normal. Screening for monoclonal gammopathy, BK viremia and circulating donor-specific antibodies, was negative.

Dense deposit disease complicated with choroidal neovascularization.

Dense deposit disease complicated with choroidal neovascularization.

Sausage on a string – two interesting case reports of dense deposit disease

Sausage on a string – two interesting case reports of dense deposit disease

C3 glomerulopathy in children: experience at a resource-limited center.

In children, C3 glomerulopathy (C3G) is a heterogeneous disease characterized by diverse clinicopathological profiles and kidney outcomes. However, diagnostic work-up in resource-limited settings is challenging because of the unavailability of complement assays and limited access to electron microscopy or genetic testing. This study aimed to describe the clinicopathological features and response to immunosuppression and evaluate renal outcomes among children with C3G in a resource-limited setting. This retrospective cohort study involved a review of the hospital records of 46 children (2013-2021) diagnosed with C3G on kidney biopsy. Their clinical, laboratory, treatment, and outcome details at onset and follow-up were noted. The mean (SD) age was 9 (4) years. The common presentation was acute nephritis (27 [58.6%]), while one in five (19.5%) presented with rapidly progressive glomerulonephritis. Focal-crescentic glomerulonephritis (14 [30.4%]) was the common histological pattern. Electron microscopy was performed in 22 (47.8%), of which 17 were C3 glomerulonephritis (C3GN) and four were dense deposit disease (DDD). None of the patients underwent complement assay or genetic testing. Almost two-thirds (63%) received empirical immunosuppressive therapy, most commonly steroids. Of the 31/46 who completed follow-up (median [IQR] duration, 11.5 [6-24] months), six (19.4%) demonstrated complete kidney recovery, while the other 25 (80.7%) had kidney sequelae; of them, five (16.1%) progressed to end-stage kidney disease and two (4.3%) died by the last follow-up. Pediatric C3G has a variable clinicopathological spectrum, while DDD is less common. Most patients present with glomerulonephritis and significant morbidities. The lack of genetic and C3Nephritic factor testing is a barrier to the comprehensive phenotyping and management of C3G in resource-limited settings.

Dynamic response analysis of monopile-supported offshore wind turbine on sandy ground under seismic and environmental loads

Monopiles are the most widely adopted foundation type for Offshore Wind Turbines (OWTs) in shallow waters. With the expansion of the construction of OWT, the number of OWT farms in seismic regions increases globally including the coastal areas of Japan and China. It is necessary to evaluate the impact of earthquakes including the vibration and soil liquefaction on the OWTs supported by the monopile foundation, while the effects of liquefaction on offshore structures, especially for OWTs with monopiles, have not been sufficiently studied. This study investigates the seismic response of the monopile-supported OWTs with the use of an advanced soil model. A three-dimensional numerical model is built, and dynamic analyses are carried out using the OpenSees framework. The pressure-dependent multi-yield (PDMY03) constitutive model is used to simulate the dynamic soil behavior. The applicability of the large-diameter pile modeling method for proper soil-pile interaction modeling in this numerical analysis is first validated through centrifuge tests on monopiles subjected to lateral loading. The dynamic analyses are then carried out to demonstrate the seismic response of the entire OWT system. The numerical results indicate that the contribution of higher modes of vibration is becoming of increased importance for large wind turbines and soil-structure interaction plays a significant role in the dynamic response. Moreover, the monopile-supported OWT in dense sand deposits experiences substantial lateral displacement and rotation under the combined action of wind and earthquake loads when liquefaction occurs.

C3 glomerulopathy in children: a European longitudinal study evaluating outcome.

C3 glomerulopathy is a rare clinical entity characterized by dysregulation of the alternative complement pathway in glomerular disease. Studies defining the natural history of C3G in the pediatric population are scarce. Patients included in this retrospective study were diagnosed between 2011 and 2020 in 12 European pediatric nephrology units. Data were collected from baseline, 6months, 12months and at the last follow-up. Complete remission (CR) was defined as a urinary protein creatinine ratio (UPCR) < 0.3mg/mg with normal estimated glomerular filtration rate (eGFR). Partial remission was defined as a decrease in UPCR to 0.3 and 3mg/mg with normal eGFR. Lack of remission was defined as non-response. A total of 108 pediatric patients were included. Complete remission was achieved in 71/108 patients (65.7%), with probability of CR of 50% at 1.8years and of 78% at 7years. At presentation by univariate analysis the predictive factors at presentation associated with CR included eGFR (p = 0.028), UPCR (p = 0.004), serum C3 levels (p = 0.018), elevated plasma sC5b9 levels, defined as > 400ng/ml, (p = 0.037), the presence of endocapillary proliferation (p = 0.017), and the absence of dense deposits on electron microscopy (p = 0.032). By multivariate analysis a low UPCR at presentation (p < 0.001) and the presence of endocapillary proliferation (p < 0.01) remained positively associated with CR. Our data confirm that C3G has a more benign outcome in children compared to previous reports in adults, and suggest that endocapillary proliferation and the degree of proteinuria at onset are the most relevant prognostic factors.

(Digital Presentation) Effects of the Morphological Changes Associated with a Li Metal Anode on Deposition and Dissolution Cycle in Bis(fluorosulfonyl)Amide-Based Ionic Liquids

Lithium metal has been considered as a promising candidate for the negative electrode of secondary batteries for several decades because its capacity (3860 mAh g–1) is higher than those of currently used electrode materials. However, the lithium metal anode has been known to exhibit poor cycle performance or give rise to short circuits due to the dendritic or whisker-like morphology of lithium formed during deposition and dissolution. Analysis of the morphology of lithium deposits, especially the cross-section, is considered to be important for contributing to research on improving the charge-discharge ability of lithium metal anode. The formation of a uniform and highly Li+conductive solid electrolyte interphase (SEI) on the lithium metal surface leading to dense and low porosity lithium deposits and a reversible deposition-dissolution reaction of lithium is a significant challenge. It has been suggested that the bis(fluorosulfonyl)amide (FSA–)-derived SEI in ionic liquid (IL) electrolyte containing a high concentration of LiFSA can improve cycle performance and suppress dendritic growth [1,2]. We have reported the cycle performance of lithium and the formation of a SEI for electrolytes comprised of LiFSA in MOEMPFSA (MOEMP+: 1-methyl-1-methoxyethylpyrrolidinium) or BMPFSA (BMP+: 1-methyl-1-butylpyrrolidinium) [3]. The resistance of the SEI in LiFSA-MOEMPFSA (1:1 molar ratio) was lower than that in LiFSA-BMPFSA (1:1 molar ratio), and the deposition and dissolution performance of a lithium metal anode was improved in LiFSA-MOEMPFSA compared to LiFSA-BMPFSA. This is thought to be due to the variation in SEI composition with IL cation structure. Previous studies have demonstrated the cycle performance at a capacity of 1 or 4 mAh cm–2 [3,4] for lithium metal. However, these values are rather low when considering the proposed application as a negative electrode material for next-generation batteries, and it is essential to study a larger capacity. In the present study, the morphological changes of Li during deposition and dissolution cycle at 10 mAh cm–2 and the relationship between cycle performance and the morphology of deposited Li was investigated. The electrolytes were prepared by mixing MOEMPFSA or BMPFSA and LiFSA at 50.0-50.0 mol%. The water contents in the ionic liquid electrolytes were less than 50 ppm, as determined by Karl Fischer titration. The preparation of 10 mAh cm–2 deposited Li on Cu was conducted using a Cu|Li planar electrode cell (laminate-like) at 0.1, 0.5 and 1.0 mA cm–2. Celgard 3501 was used as the separator. The cross-sections of the deposited lithium on Cu were revealed by processing with Ar ion milling at –80 °C. The observation of the cross-section of deposited lithium on Cu was carried out with a scanning electron microscope (SEM) with energy dispersive X-ray spectroscopy (EDX) and without exposure to air. The SEM images of the cross-sections of a 10 mAh cm–2 lithium deposit on Cu at 0.1 or 0.5 mA cm–2 in LiFSA-MOEMPFSA reveal a denser and lower porosity than that at 1.0 mA cm–2. It is suggested that columnar growth of lithium was observed due to particle growth rather than nucleation at lower current density. The morphology of the 10 mAh cm–2 lithium deposits on Cu at 0.5 mA cm–2 in LiFSA-MOEMPFSA was denser than that in LiFSA-BMPFSA. This is thought to be due to the differences in the resistance of the SEI derived from MOEMPFSA and BMPFSA. The denser and lower porosity deposited lithium is considered to be promising for operation at as high a capacity as 10 mAh cm–2, and is expected to contribute to the improvement of the reversibility of the lithium anode with suppressing dendritic growth.AcknowledgmentsThis study was supported by the Green Technologies of Excellence (GteX, JPMJGX23S0) program of the Japan Science and Technology Agency (JST). MOEMPCl was supplied by Nisshinbo Holdings Inc.References R. Furuya, T. Hara, T. Fukunaga, K. Kawakami, N. Serizawa, and Y. Katayama, J. Electrochem. Soc., 168, 100516 (2021).G. Girard, M. Hilder, N. Dupre, D. Guyomard, D. Nucciarone, K. Whitbread, S. Zavorine, M. Moser, M. Forsyth, D. MacFarlane, and P. Howlett, ACS Appl. Mater. Interfaces, 10, 6719 (2018).N. Serizawa, R. Yamashita, and Y. Katayama, J. Phys. Chem. C, 127, 10434 (2023). Y. Maeyoshi, K. Yoshii, and H. Sakaebe, J. Electrochem. Soc., 90, 047001 (2022).

Subclinical acute tubular necrosis potentially associated with red yeast rice consumption unexpectedly detected in a patient with membranous nephropathy.

In March 2024, a significant public health issue involving red yeast rice supplements emerged in Japan, which may have been associated with several health problems, including kidney dysfunction. A 74-year-old man without a history of urinary abnormalities developed nephrotic syndrome 10weeks after starting "Beni-Koji Choleste Help®," a red yeast rice supplement. Electron microscopy showed subepithelial and intramembranous dense deposits with abnormality of the glomerular basement membrane, which led to the diagnosis of long-standing membranous nephropathy. The diagnosis of phospholipase A2 receptor (PLA2R)-positive primary membranous nephropathy was confirmed via PLA2R-positive immunostaining. Furthermore, there were findings of focal tubular necrosis without unexplained cellular infiltration. Based on previous reports, it was suggested that red yeast rice-related products have triggered the acute tubular necrosis in the patient. His nephrotic syndrome reached partial remission with oral administration of prednisolone at an initial dose of 40mg/day. This case indicates that membranous nephropathy was coincidentally accompanied by acute tubular necrosis that was potentially associated with red yeast rice-related health foods. It may be reasonable to state that individuals consuming red yeast rice-related health products may develop subclinical focal tubular necrosis even in the absence of overt clinical symptoms or laboratory abnormalities. The currently recognized health issues associated with red yeast rice-related health foods may only represent a small portion of the overall risks.

The Difficulties of Treating Complement-3-Mediated Glomerulopathy.

C3 glomerulopathy (C3G) is a rare disease affecting the complement alternative pathway, categorized into dense deposit disease and C3 glomerulonephritis. Dense deposit disease predominantly affects younger individuals, while C3 glomerulonephritis tends to manifest in older populations. The diseases are characterized by dysregulation of the complement alternative pathway, leading to the deposition of complement components in the glomeruli and subsequent renal dysfunction. Notably, the incidence of C3G in the United States is low, with 1-3 cases per 1,000,000 and a prevalence of 5 cases per 1,000,000. Numerous uncertainties persist in comprehending the etiology and pathophysiology of C3G. While biomarkers such as C3 nephritic factor, autoantibodies, and relevant genetic mutations have been identified, their pathogenicity and clinical utility remain unclear. Standard workups involve complement assays and autoantibody panels, yet the definitive diagnostic test remains a kidney biopsy. Nuanced challenges lie in deciphering the sensitivity and specificity of these diagnostic tools, especially in the presence of phenotypical variations among individuals. Current therapeutic approaches, albeit lacking robust evidence, encompass a spectrum ranging from supportive care to targeted B-cell therapy and immunosuppression with mycophenolate mofetil and glucocorticoids. For severe and refractory cases, the monoclonal antibody eculizumab, targeting C5 in the complement cascade, is recommended. These treatments, while offering some relief, pose challenges related to their cost and obtaining insurance approval. Exploratory avenues delve into the potential of plasma exchange and innovative treatments such as oral complement inhibitors, reflecting the ongoing quest for effective therapeutic modalities. Trials investigating various complement inhibitors underscore the dynamic landscape of therapeutic advancements in C3G management. In conclusion, the article highlights the complexities of C3G management. The need for further understanding, large-scale trials, and ongoing investigations into disease etiology and pathophysiology is emphasized.

Initial Stages of Electrocrystallization of Coatings with Tin and Tin-Copper and Tin-Copper-Ultradisperse Diamond Alloys

The need of modern microelectronics in the development of technological processes for the formation of nanostructured layers puts forward the necessity of understanding the mechanisms of nucleation and growth of deposits. The article considers the features of the initial stages of electrocrystallization of coatings with tin and tin-copper and tin-copper-ultradisperse diamond alloys. The kinetic regularities of electrode processes were studied by the voltammetry method. Based on the experimental data, the nucleation parameters (nucleation energy, effective interphase surface energy, radius and volume of the nucleus) were calculated. SEM images were obtained and the features of the roughness of the coating surfaces after deposition for 10, 20, 30 and 60 s were studied. It was found that co-deposition of tin-copper alloys and tin-copper-ultradisperse diamond particles increases the value of the limiting current from 2.8 · 10–2 to 5.0 · 10–2 A/cm2. With an increase in electrocrystallization over-voltage, the rate of nucleation increases and their size decreases, while fine-grained and dense deposits are formed. With an increase in the deposition duration, crystallites grow and gradually coalesce with each other, the value of the equivalent diameter of the grain coatings increases, respectively, for: Sn – from 1 ⋅ 10–6 to 4 ⋅ 10–6 m, Sn-Cu – from 0.3 ⋅ 10–6 to 1.3 ⋅ 10–6 m, Sn-Cu-ultradispersed diamond – from 0.9 ⋅ 10–6 to 1.4 ⋅ 10–6 m. The established patterns make it possible to control the structure of the coatings and obtain deposits with specified properties. The presented results may be of interest to specialists involved in the formation of solderable galvanic coatings.

Effect of cathodic current density on hydrogen embrittlement susceptibility of X70 steel girth weld in different soil simulation solutions

PurposeIn this paper, the authors aim to study the relationship between hydrogen embrittlement (HE) susceptibility and cathodic current density applied on the X70 steel girth welds.Design/methodology/approachThe HE susceptibility of X70 steel girth welds were investigated through slow strain rate tensile test and observed and analyzed by optical microscope and scanning electron microscope methods.FindingsThe results show that HE susceptibility of X70 girth weld was basically unchanged with increasing of ion concentration while gradually increased and maintain at a specific value with the increase of cathodic current density. As for same ion content, a dense calcareous deposit layer generated on the sample surface in soil simulation solution with Ca2+ and Mg2+ resulted a decreased HE susceptibility while the porous calcareous deposit layer resulted a increased HE susceptibility.Originality/valueA logistic regression model was established to describe the correlation between HE index and the cathodic current density.

Novel Therapy for Recurrent Dense Deposit Disease in an Adolescent Kidney Transplant Recipient

Novel Therapy for Recurrent Dense Deposit Disease in an Adolescent Kidney Transplant Recipient

Rapidly Progressive Glomerulonephritis Due to Dense Deposit Disease Overlapping Alport Syndrome

Rapidly Progressive Glomerulonephritis Due to Dense Deposit Disease Overlapping Alport Syndrome

Fibronectin glomerulopathy in an elderly patient with FN1 gene mutation: a case report and literature review

BackgroundFibronectin glomerulopathy (FNG) is a rare autosomal dominant glomerulopathy that can lead to nephrotic syndrome. Here we report the case of an elderly patient diagnosed with FNG, exhibiting nephrotic-range proteinuria, with a 2-year follow-up.Case presentationA 75-year-old Korean female visited the nephrology clinic after experiencing generalized edema for 2 months. Her serum creatinine was 1.36 mg/dL, and urine protein-to-creatinine ratio was 3.99 g/g. Kidney biopsy revealed mesangial and subendothelial dense deposits, and immunohistochemistry for fibronectin showed strong positivity in the glomerulus. The patient’s family history included non-specific renal disease in her mother and two siblings. Genetic testing of the fibronectin 1 (FN1) gene showed Y973C mutation. She received conservative treatment, including angiotensin II receptor blockers (ARB). Two years after biopsy, the patient has preserved renal function and reduced proteinuria.ConclusionWe report the case of a 75-year-old patient with nephrotic-range proteinuria, who was diagnosed with FNG, and found to harbor a FN1 gene mutation. In this case, conservative treatment including ARB yielded reduction of proteinuria and preservation of renal function.

Molten Salt Electrodeposition: Review

Molten salt electrodeposition is the process of producing impressively dense deposits of refractory metals using the electrolysis of molten salts. However, predicting which electrochemical parameters and setup will best control different kinds of deposition (density, homogeneity, etc.) is an ongoing challenge, due to our limited understanding of the properties and mechanisms that drive molten salt electrodeposition. Because these advancements have been made rapidly and in different arenas, it is worth taking the time to stop and assess the progress of the field as a whole. These advancements have increasing relevance for the energy sector, the development of space materials and engineering applications. In this review, we assess four critical facets of this field: (1) how the current understanding of process variables enhances the electrodeposition of various molten salts and the quality of the resulting product; (2) how the electrochemical setup and the process parameters (e.g., cell reactions) are known to impact the electrodeposition of different metal coatings and refractory-metal coatings; (3) the benefits and drawbacks of non-aqueous molten salt electrodeposition, and (4) promising future avenues of research. The aim of this work is to enhance our understanding of the many procedures and variables that have been developed to date. The expectation is that this review will act as a stimulant, motivating scientists to delve further into the investigation of refractory-metal alloys by utilizing molten salt electrodeposition.

Membranoproliferative Glomerulonephritis over 20 Years at a Tertiary Referral Center in the UK

Introduction: Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury seen on kidney biopsy, with various underlying etiologies. The component types, including complement-mediated MPGN, are relatively rare. This study presents longitudinal real-world data over 20 years in a tertiary renal center in the UK. Methods: All patients with an MPGN pattern on kidney biopsy between 2000 and 2020 were identified. After applying exclusion criteria, 38 patients remained. Data including patient demographics, details of the renal histology from the kidney biopsy, baseline laboratory results, treatments received, and clinical outcomes including renal replacement therapy and death were collected from the organization’s electronic patient record. Results: Twenty-eight of the cohort had immune complex-mediated MPGN, and 10 had complement-mediated MPGN (8 with C3 glomerulonephritis and 2 with dense deposit disease). Median follow-up was 72 months. Median age was 61 years. Overall, 60.5% were female, and 92.1% white. At presentation, median eGFR was 31.5 mL/min/1.73 m2 and uPCR 394 mg/mmol. Here, 78.9% received renin-angiotensin-aldosterone system inhibitors and 71.1% received any immunosuppression. In total, 47.4% progressed to ESKD and 50% died during follow-up. Conclusions: The study found an older patient population than typically reported. Poor outcomes were observed in the overall cohort with progression to ESKD and mortality both at almost 50%. This may be influenced by the older patient population. Individualized management of patients with an MPGN biopsy finding is paramount, with comprehensive evaluation for triggers and complement abnormalities. Going forward, registry enrolment and collaborative studies may enhance knowledge and outcomes.

Multimodal Imaging of Bilateral Retinal Pigment Epithelial Immunoglobulin Light Chain Deposition in Patients with Systemic Immunoglobulin Light Chain Deposition

ObjectiveTo describe multimodal imaging of peculiar bilateral globular subretinal deposits and acquired serous retinal detachment in patients with systemic immunoglobulin light chain deposition. DesignA retrospective observational case series. ParticipantsWe examined six eyes in three patients (one with multiple myeloma, one with membranous nephropathy, and one with immunoglobulin A nephropathy) at the Eye and ENT Hospital of Fudan University. The patients presented with peculiar globular subretinal deposits along the retinal pigment epithelium (RPE)‒Bruch’s membrane complex and acquired serous retinal detachment. MethodsFundus appearance was documented with multimodal imaging, which included fundus photography, fundus autofluorescence, spectral domain optical coherence tomography (OCT), swept-source OCT (SS-OCT), en-face OCT, and SS-OCT angiography. Additional evaluations included serum protein electrophoreses, positron emission tomography computed tomography, and renal and bone biopsies to assess the primary diseases. Main Outcome MeasuresMultimodal imaging, course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. ResultsBilateral, multiple, speckled, or patchy RPE changes in the posterior fundus that corresponded to striking multifocal hyperautofluorescence on fundus autofluorescence and lumpy, globular hyperreflective deposits along the RPE‒Bruch’s membrane complex were identified as characteristic features of bilateral RPE light chain deposition. These features may be accompanied by dense light chain deposits in the choriocapillaris and choroid vessels, diffuse choroidal thickening, and “angiographically silent” serous retinal detachment in patients with systemic immunoglobulin light chain deposition. ConclusionsWe have documented the characteristic features, clinical course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. Appropriate evaluations, including serum protein electrophoresis and hematologic consultation, are recommended to manage patients with this fundus abnormality.