Retinal Pigment Epithelium Changes Research Articles

PRPH2-associated Retinal Diseases: A Systematic Review of Phenotypic Findings

PurposePRPH2-associated retinal diseases (PARD) result from pathogenic PRPH2 variants, primarily affecting photoreceptor outer segments and retinal pigment epithelium. The focus of this article is to review and discuss the phenotyping of PARD subtypes. DesignA systematic review MethodsThe review followed PRISMA 2020 guidelines with searches on PubMed, Medline, Web of Science, Google Scholar, and Cochrane Library. Eligible studies were those which discussed molecularly confirmed PARD or described associated diseases such as butterfly pattern dystrophy. Inclusion: cross-sectional, cohort, case-control studies, book chapters. Exclusion: non-English, conference papers, non-peer-reviewed, or non-full text articles. ResultsPARD is responsible for 25% of pattern dystrophy and up to 5% of inherited retinal dystrophies. There is clear evidence of phenotypic variability between individuals carrying the same pathogenic variant. Fundus autofluorescence, fluorescein angiography, optical coherence tomography, while in research adaptive optics reveal detailed phenotypic characteristics, notably in retinal pigment epithelium changes and photoreceptor disruption. The phenotypic of PARD variability presents diagnostic challenges, with phenotypic features often overlapping with other retinal diseases including age-related macular degeneration, Stargardt disease and retinitis pigmentosa. ConclusionThis review emphasizes revising diagnostic criteria by incorporating more recent imaging techniques and confirming diagnosis with the use of genetic testing. Understanding phenotypic diversity and intrafamilial variability in PARD is crucial for developing new treatments and for patient prognosis and future research should focus on larger cohorts studying genotype-phenotype correlations.

Autosomal dominant macular dystrophy linked to a chromosome 17 tandem duplication.

Hereditary Macular Dystrophies (HMDs) are a genetically diverse group of disorders that cause central vision loss due to photoreceptor and retinal pigment epithelium (RPE) damage. We investigated a family with a presumed novel autosomal dominant HMD characterized by faint, hypopigmented RPE changes involving the central retina. Genome and RNA sequencing identified the disease-causing variant to be a 560 kilobase tandem duplication on chromosome 17 [NC_000017.10 (hg19): g.4012590_4573014dup], which led to the formation of a novel ZZEF1-ALOX15 fusion gene, that upregulates ALOX15. ALOX15 encodes a lipoxygenase involved in polyunsaturated fatty acid metabolism. Functional studies showed retinal disorganization, and photoreceptor and RPE damage following electroporation of the chimera transcript in mouse retina. Photoreceptor damage also occurred following electroporation with a native ALOX15 transcript but not with a near-null ALOX15 transcript. Affected patients' lymphoblasts demonstrated lower levels of ALOX15 substrates and an accumulation of neutral lipids. We implicated the fusion gene as the cause of this family's HMD, due to mis-localization and overexpression of ALOX15, driven by the ZZEF1 promoter. To our knowledge, this is the first reported instance of a fusion gene leading to HMD or inherited retinal dystrophy, highlighting the need to prioritize duplication analysis in unsolved retinal dystrophies.

6609 Central Serous Chorioretinopathy in the Eyes of the Beholder of Testosterone Depot Injection

Abstract Disclosure: H. Ni: None. D. Kankanamge: None. J. Jabbour: None. V.A. Preda: None. Background: Central serous chorioretinopathy (CSC) is a characterised by subretinal fluid accumulation causing detachment of the neurosensory retina and visual disturbance[1]. It has been postulated that increased focal choriocapillaris permeability results in leakage of interstial fluid into the subretinal space[1]. CSC is a rare side effect of testosterone therapy, the exact mechanism is unclear. Case : We present a 32-year-old male gym manager who has been self-administering anabolic steroids with testsoterone ethanoate IM injections every 14 days for body building. He reported left blurred vision for 8 weeks. He was normotensive and reported taking doxycycline and azithromycin for mycoplasma genitalia. There was no history of glucocorticoid exposure, smoking, alcohol use, gastoesophageal reflux disease, hypertension, shift work, sleep apnoea, nor other established risk factors for CSC. The visual acuity was OD 6/6 and OS 6/9 with intraocular pressures of 12mmHg on the right and 15mmg on the left. Fundoscopy revealed a left serous macular elevation involving the left fovea. A macular OCT confirmed the left acute central serous chorioretinopathy and right retinal pigment epithelial changes. The latter were suggestive of right CSC in the past. Discussion: Androgens have been associated with CSC in the literature. It has been hypothesised that exogenous testosterone may cause increased choriodal blood flow and permeability, promote atheroscleorsis, cause sodium retention and potentially interact with retinal pigment epithelium (RPE) via androgen receptors4. Intramuscular testosterone therapy causes fluctuation in plasma testosterone concentration (which is thought to be more relevant than absolute value of testosterone). Most cases (60%) of CSC resolve spontaneously, and appear to coincide with cessation of testosterone therapy5. Conclusion: Clinicans need to be alert to the use of testosterone and other anabolic steroids, prescribed or self administered, particularly in their patients with CSC or who have other risk factors for CSC, such as corticosteroids, smoking and hypertension.

Sodium-iodate injection can replicate retinal and choroid degeneration in pigmented mice: Using multimodal imaging and label-free quantitative proteomics analysis

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO3), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO3-treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO3 injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO3-treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood.

Multimodal imaging analysis of autosomal recessive bestrophinopathy: Case series.

Autosomal recessive bestrophinopathy (ARB) is a subtype of bestrophinopathy caused by biallelic mutations of the BEST1 gene, which affect the retinal pigment epithelium (RPE). Studying RPE abnormalities through imaging is essential for understanding ARB. This case series involved the use of multimodal imaging techniques, namely autofluorescence (AF) imaging at 488 nm [short-wavelength AF] and 785 nm [near-infrared AF (NIR-AF)] and polarization-sensitive optical coherence tomography (PS-OCT), to investigate RPE changes in 2 siblings with ARB. Two Japanese siblings (Case 1: male, followed for 20-23 years; Case 2: female, followed for 13-17 years) carried compound heterozygous mutations of the BEST1 gene. Both siblings were diagnosed with ARB. Multimodal imaging techniques were used to evaluate RPE changes. Both siblings had funduscopic changes similar to those seen in the vitelliruptive stage of Best vitelliform macular dystrophy during the follow-up period. NIR-AF imaging showed hypo-AF of the entire macular lesion in both cases, and this hypo-AF remained stable over time. PS-OCT confirmed reduced RPE melanin content in these hypo-AF areas. Additionally, hyper-NIR-AF dots were observed within hypo-NIR-AF areas. Concomitant identification of focally thickened RPE melanin on PS-OCT imaging and hyper-AF on short-wavelength AF imaging at the sites containing hyper-NIR-AF dots indicated that the hyper-NIR-AF dots had originated from either stacked RPE cells or RPE dysmorphia. We confirmed RPE abnormalities in ARB, including diffuse RPE melanin damage in the macula alongside evidence of RPE activity-related changes. This case series demonstrates that multimodal imaging, particularly NIR-AF and PS-OCT, provides detailed insights into RPE alterations in ARB.

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.

IGF2BP2 Maintains Retinal Pigment Epithelium Homeostasis by Stabilizing PAX6 and OTX2.

N6-methyladenosine (m6A) methylation is a chemical modification that occurs on RNA molecules, where the hydrogen atom of adenine (A) nucleotides is replaced by a methyl group, forming N6-methyladenosine. This modification is a dynamic and reversible process that plays a crucial role in regulating various biological processes, including RNA stability, transport, translation, and degradation. Currently, there is a lack of research on the role of m6A modifications in maintaining the characteristics of RPE cells. m6A readers play a crucial role in executing the functions of m6A modifications, which prompted our investigation into their regulatory roles in the RPE. Phagocytosis assays, immunofluorescence staining, flow cytometry experiments, β-galactosidase staining, and RNA sequencing (RNA-seq) were conducted to assess the functional and cellular characteristics changes in retinal pigment epithelium (RPE) cells following short-hairpin RNA-mediated knockdown of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). RNA-seq and ultraviolet crosslinking immunoprecipitation with high-throughput sequencing (HITS-CLIP) were employed to identify the target genes regulated by IGF2BP2. adeno-associated virus (AAV) subretinal injection was performed in 6- to 8-week-old C57 mice to reduce IGF2BP2 expression in the RPE, and the impact of IGF2BP2 knockdown on mouse visual function was assessed using immunofluorescence, quantitative real-time PCR, optical coherence tomography, and electroretinography. IGF2BP2 was found to have a pronounced effect on RPE phagocytosis. Subsequent in-depth exploration revealed that IGF2BP2 modulates the mRNA stability of PAX6 and OTX2, and the loss of IGF2BP2 induces inflammatory and aging phenotypes in RPE cells. IGF2BP2 knockdown impaired RPE function, leading to retinal dysfunction in vivo. Our data suggest a crucial role of IGF2BP2 as an m6A reader in maintaining RPE homeostasis by regulating the stability of PAX6 and OTX2, making it a potential target for preventing the occurrence of retinal diseases related to RPE malfunction.

Retinal dystrophy associated with Birt-Hogg-Dubé syndrome

Purpose: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant cancer syndrome characterized by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax, and multifocal renal carcinomas. Ophthalmologic findings associated with BHDS include flecked chorioretinopathy, choroidal melanoma, iris melanocytosis, and eyelid fibrofolliculomas. We present the case of a retinal dystrophy associated with BHDS. Methods: Observational case report. Results: A 48-year-old woman was referred for poor night vision and peripheral visual field loss. She had a past medical history of Birt-Hogg-Dubé syndrome, manifesting as multiple pulmonary cysts and atelectasis of both lungs. Best corrected visual acuity was 20/25 OU. Posterior segment examination revealed significant vessel attenuation and peripheral retinopathy consistent with a retinal dystrophy. Conclusion: This case associates BHDS with retinal pigment epithelial changes and visual field defects. Patients with BHDS should undergo ophthalmological examination as part of their care.

Первый опыт применения субпорогового наносекундного лазерного воздействия при промежуточной форме возрастной макулярной дегенерации

Purpose. To present a clinical case of the first experience of subthreshold nanosecond laser treatment for an intermediate age-related macular degeneration (AMD). Methods. A 70-year-old patient T. diagnosed with intermediate AMD, underwent subthreshold nanosecond laser exposure using a 2RT device (Ellex, Australia). The patient underwent multimodal diagnostics, including best-corrected visual acuity (BCVA) measurement, fundus ophthalmoscopy, short-wave and infrared autofluorescence, infrared light imaging, multispectral laser scanning and optical coherence tomography at the baseline, 1- and 3-month follow-up. Results. No significant changes were observed at 1-month follow-up. 3 months after 2RT, the patient noted a subjective improvement in the contrast and quality of vision, while BCVA increased from 0.7 to 0.8. When performing OCT scans in followup mode, the disappearance of a number of large confluent drusen in the area nasal to the fovea was noted. A decrease in retinal thickness was also observed in this area due to the resorption of large confluent drusen. The infrared imaging and autofluorescence showed no changes in retinal pigment epithelium and no appearance hypoautofluorescence of atrophic zones. Conclusion. The first experience of subthreshold nanosecond laser treatment of intermediate AMD revealed a potential positive functional and structural outcome in case of the presence of large confluent drusen. Further studies with a larger number of patients are needed. Key words: subthreshold nanosecond laser exposure, age-related macular degeneration, confluent drusen

Type 1 and type 2 torpedo maculopathy.

To analyze torpedo maculopathy (TM) and to report the characteristics of the disease. Retrospective study. The review of a database for clinical diagnosis identified eight patients with TM lesions in the retina between 2016 and 2022. Multimodal imaging was used to analyze the cases. All cases were unilateral, asymptomatic, and hypopigmented. They were associated by surrounding hyperpigmented retinal pigment epithelium changes to varying degrees. All lesions were located in the temporal retina on the horizontal axis, pointing towards the fovea, except for one patient with a lesion inferior to the fovea. Optical coherence tomography imaging revealed a normal inner retina in all eyes. In the area of the TM lesion, attenuation of the interdigitation zone was seen in mild cases (three cases). All other five patients had thinning of the outer nuclear layer and loss of ellipsoid zone and interdigitation zone of the TM lesion. Four of these cases had a subretinal cavitation/cleft, and two of them additionally an inner choroidal excavation. No patient had any sign of choroidal neovascularization. The average age for patients with type 1 TM was 18years and for type 2 TM 16.5years. In this large case series, we could not detect an age difference between the different types of the TM. Contrary to previous discussions, type 2 TM can also occur in young patients.

Ultrastructural changes in the rat retina in the presence of long-term opioid exposure

Purpose: To determine the features of the untrastructural reorganization in the rat retina by the end of week 4 and week 6 of experimental opioid exposure. Material and Methods: Forty-eight adult male albino rats (weight, 200-250 g; age, 4.5 months) were used in this study. They received nalbuphine hydrochloride intramuscularly daily for 42 days. Particularly, the drug was administered daily at a dose of 0.212 mg/kg for weeks 1 and 2, 0.225 mg/kg for weeks 3 and 4, and 0.252 mg/kg for weeks 5 and 6. In this way, we experimentally created the conditions of chronic opioid exposure. Animals were divided into three groups. Group 1 (19 animals) received nalbuphine for 28 days, and group 2 (19 animals), for 42 days. Group 3 (control group) comprised 10 animals. Of these, 5 animals were treated with normal saline at a dose of 0.22 mg/kg intramuscularly daily for 28 days, and the rest were treated in a similar manner for 42 days. Transmission electron microscopy studies of the rat retina were conducted in a routine manner. Results: By the end of week 4 of experimental opioid exposure, there was an increase in the number of retinal microvessels with signs of hyperemia and degenerative changes in retinal pigment epithelium (RPE) cells, increase in the destruction of membranous discs of photoreceptor outer segments, necrobiotic changes in the nuclei of individual photoreceptors, axonal degeneration in the outer and inner plexiform layers, degenerative changes in retinal horizontal neurons, and the appearance of necrotic structural changes in the cytoplasm of bipolar and amacrine cells. By the end of week 6, there was a further increase in hyperemia of retinal vessels and degenerative and necrotic changes in individual RPE cells and photoreceptor outer segments. In addition, we observed destruction and shortening of mitochondrial cristae of photoreceptor inner segments, necrotic nuclear changes in individual photoreceptors, degeneration of axons of the outer and inner plexiform layers, degenerative and necrotic changes in bipolar and amacrine cells, hypertrophic Müller cell processes, degeneration of ganglion cells, and vascular hyperemia and moderate perivascular edema in the outer and inner plexiform layers. Conclusion: Therefore, in the current rat study, after a 4-week exposure to daily nalbuphine injections at a dose ranging 0.212 to 0.253 mg/kg, there was ultrastuctural evidence of destructive processes in the RPE and photoreceptor outer segments, axonal degeneration in the outer and inner plexiform layers, degenerative and necrotic changes in bipolar and amacrine cells, hypertrophic Müller cell processes, ganglion cell degeneration and hyperemia due to an impaired retinal microcirculatory ultrastructure. At week 6 of the experiment, there was evidence of increased destructive and degenerative processes in structural components of the retina.

Bilateral choroidal haemangioma in an otherwise normal middle aged female

Circumscribed choroidal hemangioma is a rare benign vascular tumor. It is of two types, circumsribed and diffuse. Circumscribed choroidal hemangioma is a well demarcated solitary lesion, usually situated posterior to equator, while diffuse have ill defined thickening of choroid involving more than one zone or quadrant. Patient may present with progressive diminution of vision, metamorphopsia, floaters and visual field defect. The visual symptoms are because of associated subretinal fluid, cystoid macular edema, and in long standing cases, retinal pigment epithelium changes, subretinal fibrosis and retinoschisis. It must be distinguished from amelanotic melanoma and choroidal metastasis. Investigation such as ultrasound, optic coherence tomography, fundus fluorescein angiography, indocyanin green angiography can be used to confirm the diagnosis. Multiple treatment options like transpupillary thermotherapy, photodynamic therapy, plaque brachytherapy and external beam radiotherapy.

Multimodal Retinal Imaging Findings in Hardikar Syndrome.

To describe the syndromic, clinical, and retinal findings of a patient with an extremely-rare genetic condition known as Hardikar Syndrome (HS) with presentation of optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiographic (FA), and indocyanine green angiographic (ICG) findings. Clinical course was detailed and followed over time with examinations and multimodal imaging. A 17-year-old patient with HS was referred for possible retinitis pigmentosa. Dilated fundoscopic examination revealed large, multifocal cauliform patches of chorioretinal retinal pigment epithelium (RPE) changes with RPE drop-out involving the macula and periphery in both eyes. Additionally, an inactive choroidal neovascular membrane (CNVM) was present in the left eye. Multimodal imaging with OCT, FAF, FA and ICG correlated with the clinical findings of focal patches of chorioretinal degeneration in both eyes. Additionally, an anomalous finding of the superior retinal arterial vessels filling in tandem with the choroidal was present in the left eye. The patient's clinical findings were consistent with HS, and genetic testing with whole exome sequencing revealed a pathogenic mutation in the MED12 gene, confirming diagnosis. HS is associated with RPE degeneration, creating focal patches of pigmentary chorioretinal atrophic lesions. Vision loss can occur due to the development of CNVMs. We recommend close evaluation and follow-up for HS patients with multimodal retinal imaging.

Association of Retinal Pigment Epithelium Reflectivity on Optical Coherence Tomography with Recurrence of Vogt-Koyanagi-Harada Disease: A Retrospective Observational Study.

Despite the necessity of optical coherence tomography (OCT) for diagnosis and longitudinal monitoring in patients with Vogt-Koyanagi-Harada (VKH) disease, no studies have identified useful OCT markers for predicting recurrence in these patients. Although the precise reason for this remains unclear, one possibility is that infiltration of inflammatory cells into the choroid attenuates the OCT signal, making it difficult to precisely assess the structure of the choroid. Therefore, this study aimed to investigate changes in retinal pigment epithelium (RPE) reflectivity immediately above the choroid in eyes with acute VKH disease, as well as the association between RPE reflectivity and VKH disease recurrence. This single-centered retrospective observational study included 20 treatment-naïve patients with acute VKH disease presenting with serous retinal detachment (SRD) in the posterior pole at the initial visit between October 2015 and January 2020, as well as 15 healthy control eyes. All patients were followed up for at least 6 months and received treatment with intravenous methylprednisolone followed by oral administration of prednisolone. Swept-source OCT images through the fovea were used to measure central retinal thickness, central choroidal thickness, and RPE reflectivity. During an observation period of 37.2 ± 30.8 months, recurrence of inflammation was observed in 11 patients (55.0%). Initial visual acuity was worse in patients who developed recurrence than in those who did not (P=0.024). On initial OCT images, RPE reflectivity differed significantly between patients with and without recurrence (1.75 ± 0.42 vs 1.35 ± 0.20; P=0.018), while there were no significant differences in other chorioretinal parameters, such as central retinal thickness and choroidal thickness. RPE reflectivity on OCT images may be useful for predicting the recurrence of inflammation in patients with VKH disease.

Decreased perifoveal ganglion cell complex thickness - a first sign for macular damage in patients using hydroxychloroquine.

Aim: To examine ganglion cell complex (GCC) thickness detected by optical coherence tomography (OCT) in patients using hydroxychloroquine (HCQ), without any structural and functional macular changes to evaluate the initial symptoms of macular toxicity for early diagnosis before clinical evaluation. Methods: Eighty eyes of forty patients (Group 1) and forty eyes of twenty healthy volunteer persons (Group 2) were included in the study. Detailed ophthalmologic and mydriatic fundus examination were applied to all patients and volunteers (controls). Spectral domain OCT, visual field (VF) and color vision test were performed. Measurements of macula thickness, GCC thickness (involving nerve fiber layer, ganglion cell layer and inner plexiform layer) and peripapillary retinal nerve fiber layer (RNFL) were performed with OCT. Patients with retinal pigment epithelial changes, VF paracentral scotoma and defected color vision were excluded from the planned study. Results: Perifoveal GCC layer thickness in all quadrants was significantly thinner in group 1 compared to group 2 (p=0.017, p=0.001, p=0.019, p=0.001). The mean global inferior hemifield and nasal quadrant RNFL thickness were lower than in the control groups (p=0,012, p=0,009, p=0,005, respectively). Conclusion: Changes in the thickness of nerve fiber layer and ganglion cell layer detected by optical coherence tomography can be thought to be used as a diagnostic aid for the early diagnosis of hydroxychloroquine-toxic maculopathy Abbreviations: GCC = Ganglion cell complex, OCT = Optical coherence tomography, HCQ = Hydroxychloroquine, BCVA = Best-corrected visual acuity, IOP = Intraocular pressure, VF = Visual field, RNFL = Retinal nerve fiber layer, SD OCT = Spectral-domain optical coherence tomography, mfERG = Multifocal electroretinogram, FAF = Fundus autofluorescence, IS/ OS = Inner segment-outer segment junction, SITA = Swedish Interactive Threshold Algorithm, RA = Rheumatoid arthritis, SLE = Systemic lupus erythematosus, SS = Sjogren syndrome.

Central Serous Chorioretinopathy by Autofluorescence, Enface and SLO-Retromode Imaging.

The aim of our study was to investigate the clinical features of central serous chorioretinopathy (CSC) with autofluorescence (AF), retromode (RM), and enface imaging. This retrospective study was conducted at Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome (Italy), between September and December 2022. Each patient underwent a complete ophthalmological examination, which included optical coherence tomography (OCT), enface image analysis, AF, and RM imaging. We further evaluated the presence and area of extension of serous retinal detachment and retinal pigment epithelium (RPE) atrophy through AF, RM, and enface imaging. We included 32 eyes from 27 patients (mean age: 52.7 ± 13.3 years). The median AF area was 19.5 mm2 (IQR 6.1-29.3), while the median RM area was 12.3 mm2 (IQR 8.1-30.8), and the median enface area was 9.3 mm2 (IQR 4.8-18.6). RPE atrophy was diagnosed in 26 cases (81.3%) with RM imaging and in 75% of cases with AF. No difference emerged between AF and RM analysis in the detection of central serous detachment in CSC. However, RM imaging showed a high specificity (91.7%) and negative predictive value (84.6%) to detect RPE changes when compared to the AF standard-of-care technique. Thus, RM imaging could be considered an adjunctive imaging method in CSC.

Proteome changes in a human retinal pigment epithelial cell line during oxidative stress and following antioxidant treatment.

Age related macular degeneration (AMD) is the most common cause of blindness in the elderly. Oxidative stress contributes to retinal pigment epithelium (RPE) dysfunction and cell death thereby leading to AMD. Using improved RPE cell model systems, such as human telomerase transcriptase-overexpressing (hTERT) RPE cells (hTERT-RPE), pathophysiological changes in RPE during oxidative stress can be better understood. Using this model system, we identified changes in the expression of proteins involved in the cellular antioxidant responses after induction of oxidative stress. Some antioxidants such as vitamin E (tocopherols and tocotrienols) are powerful antioxidants that can reduce oxidative damage in cells. Alpha-tocopherol (α-Toc or αT) and gamma-tocopherol (γ-Toc or γT) are well-studied tocopherols, but signaling mechanisms underlying their respective cytoprotective properties may be distinct. Here, we determined what effect oxidative stress, induced by extracellularly applied tBHP in the presence and absence of αT and/or γT, has on the expression of antioxidant proteins and related signaling networks. Using proteomics approaches, we identified differential protein expression in cellular antioxidant response pathways during oxidative stress and after tocopherol treatment. We identified three groups of proteins based on biochemical function: glutathione metabolism/transfer, peroxidases and redox-sensitive proteins involved in cytoprotective signaling. We found that oxidative stress and tocopherol treatment resulted in unique changes in these three groups of antioxidant proteins indicate that αT and γT independently and by themselves can induce the expression of antioxidant proteins in RPE cells. These results provide novel rationales for potential therapeutic strategies to protect RPE cells from oxidative stress.

Randomized controlled trials in central serous chorioretinopathy: A review.

Central serous chorioretinopathy (CSCR), a common chorioretinal disease, presents with a myriad of manifestations. Acute CSCR presents with localized neurosensory detachment whereas chronic CSCR may show widespread retinal pigment epithelium (RPE) changes, chronic shallow subretinal fluid, andchoroidal neovascularization (CNV) suggestive of a variable natural history leading to suboptimal visual outcomes. Even though multiple treatment options including laser photocoagulation, photodynamic therapy, micropulse laser, anti-vascular endothelial growth factors, and systemic drugs (spironolactone, eplerenone, melatonin, mifepristone) are available, there isan absence of any standardized treatment protocol or gold standard treatment modality. Moreover, their performance compared to observation especially in acute CSCR is still debatable. Compared to other chorioretinal diseases such as age-related macular degeneration, diabetic retinopathy, diabetic macular oedema, and retinal vein occlusion, there is arelative dearth of randomized controlled trials in CSCR. Multiple inconsistencies including reliance on history of disease duration, variable inclusion criteria/disease descriptors/study endpoints, and availability of multiple treatment modalities lead to difficulties in designing RCTs. A consensus-based treatment protocol, therefore, is still elusive. We reviewed the literature and compiled the list of papers published to date, wherein we analyse and compare the inclusion criteria, imaging modalities, study endpoints, studyduration, andstudy results. Correcting these discrepancies and deficiencies will help standardize future study designs, facilitating a next step towarda standardized treatment protocol.

Long-Term Multimodal Imaging Analysis of Selective Retina Therapy Laser Lesions.

This study evaluates the long-term effects of selective retina therapy (SRT) on the retinal pigment epithelium (RPE) and neuroretina in patients with central serous chorioretinopathy. SRT was performed on 36 patients using a Nd:YLF-Laser at 527 nm (R:GEN®, Lutronic, Goyang-Si, Republic of Korea). A total of 994 titration spots were examined using up to three years' multimodal imaging. Leakage in fluorescein angiography (FA) was observed after SRT in 523 lesions and resolved after one month. SRT lesions were not visible clinically, but appeared as brightly reflective areas in infrared and multicolor images. Normal morphology was observed in optical coherence tomography (OCT) immediately after SRT. After one month, thickening of the RPE and interdigitation zone changes were seen and disappeared after 539 ± 308 days. No RPE atrophies occurred during the observation period. Decreased fundus autofluorescence (FAF) was mostly observed directly after SRT followed by increased FAF at one month, which faded over time. A significant decrease in the number of visible lesions in the FA and FAF was observed within the three-year follow-up. OCT findings are consistent with animal studies showing SRT-related defect closure by hypertrophy and migration of neighboring cells without RPE atrophy or photoreceptor damage. This suggests that SRT is a safe treatment option for macular diseases and does not lead to retinal atrophy.

Aging induces cell loss and a decline in phagosome processing in the mouse retinal pigment epithelium

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and dysfunction in the retinal pigment epithelium (RPE) with age is known to contribute to disease development. The aim of this study was to investigate how the C57BL/6J mouse RPE changes with age. RPE structure was found to change with age and eccentricity, with cell size increasing, nuclei lost, and tight junctions altered in the peripheral retina. Phagocytosis of photoreceptor outer segments (POS) by the RPE was investigated using gene expression analysis and histology. RNA-Seq transcriptomic gene profiling of the RPE showed a downregulation of genes involved in phagosome processing and histological analysis showed a decline in phagosome-lysosome association in the aged tissue. In addition, failures in the autophagy pathway that modulates intracellular waste degradation were observed in the aged RPE tissue. These findings highlight that RPE cell loss and slowing of POS processing contribute to RPE dysfunction with age and may predispose the aging eye to AMD development.