Retinal Pigment Epithelium Alterations Research Articles

Longitudinal structural changes in central serous chorioretinopathy: A multimodal imaging-based study.

To analyse the longitudinal changes in imaging parameters in eyes with acute or chronic central serous chorioretinopathy (CSCR). This was a multicentric, retrospective, longitudinal, observational study in patients with a diagnosis of CSCR and having at least 4 years of follow-up. Trend in choroidal thickness (CT), area of double layer sign (DLS), area of retinal pigment epithelium (RPE) alterations, and area of hyper-autofluorescence were analysed. A total of 175 eyes of 146 patients with a mean age of 52.9 ± 12.5 years were included. Fifty-two eyes had acute and 123 had chronic CSCR at baseline. There was an overall decreasing trend of CT values during follow up (from 354.4 ± 74.8 at baseline to 343.2 ± 109.4 at final visit). There was a steady rise in DLS width and RPE alteration in the overall cohort (from 811.7 ± 760.6 microns and 3.5 ± 3.3 disc areas respectively at baseline to 1209.1 ± 1113.18 microns, 4.1 ± 3.6 disc areas at final visit). An initial rise in hyper-autofluorescent area followed by steady fall was seen in chronic CSCR. A significant positive correlation (r = 0.54, p = 0.004) was seen between change in DLS width and change in area of hyper-autofluorescence. On linear regression analysis, lower CMT and absence of intraretinal fluid at baseline were associated with greater increase in RPE abnormalities. Acute and chronic CSCR had different pattern of change in imaging parameters with area of RPE alterations in acute CSCR not reaching values close to that of chronic CSCR eyes even after long follow up.

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.

High-resolution adaptive optics-trans-scleral flood illumination (AO-TFI) imaging of retinal pigment epithelium (RPE) in central serous chorioretinopathy (CSCR)

This study aims to correlate adaptive optics-transscleral flood illumination (AO-TFI) images of the retinal pigment epithelium (RPE) in central serous chorioretinopathy (CSCR) with standard clinical images and compare cell morphological features with those of healthy eyes. After stitching 125 AO-TFI images acquired in CSCR eyes (including 6 active CSCR, 15 resolved CSCR, and 3 from healthy contralateral), 24 montages were correlated with blue-autofluorescence, infrared and optical coherence tomography images. All 68 AO-TFI images acquired in pathological areas exhibited significant RPE contrast changes. Among the 52 healthy areas in clinical images, AO-TFI revealed a normal RPE mosaic in 62% of the images and an altered RPE pattern in 38% of the images. Morphological features of the RPE cells were quantified in 54 AO-TFI images depicting clinically normal areas (from 12 CSCR eyes). Comparison with data from 149 AO-TFI images acquired in 33 healthy eyes revealed significantly increased morphological heterogeneity. In CSCR, AO-TFI not only enabled high-resolution imaging of outer retinal alterations, but also revealed RPE abnormalities undetectable by all other imaging modalities. Further studies are required to estimate the prognosis value of these abnormalities. Imaging of the RPE using AO-TFI holds great promise for improving our understanding of the CSCR pathogenesis.

Evolution of Pentosan Polysulfate Maculopathy Following Medication Discontinuation

Purpose: To describe a patient receiving pentosan polysulfate (PPS) for interstitial cystitis, who developed PPS maculopathy (PPSM) that persisted and evolved for four years after medication discontinuation. Methods: Case report of one patient at a tertiary retina clinic. Results: A 48-year-old female with a history of interstitial cystitis was referred to our retina clinic with no vision complaints. She had been taking PPS for 10 years, first consuming 600mg/day for eight years, followed by 200mg/day for two years. At first presentation in 2016, examination revealed macular pigmentary clumping in both eyes. In subsequent years, pigmentary changes were confirmed by optical coherence tomography (OCT) which showed progressive macular thinning in both eyes. In 2019, the patient discontinued PPS; however, she continued to exhibit PPSM progression for years thereafter. At four-year follow-up after discontinuation of PPS, the patient returned with stable vision, but showed changes in macular lipofuscin deposits with outer retinal and retinal pigment epithelial alterations. Conclusion: This case demonstrates sustained and evolving PPSM even after drug discontinuation, suggesting that active PPS may have a prolonged half-life in the retina and retinal pigment epithelium.

Ayurvedic management of Dhumadarshi (central serous chorioretinopathy): A case report

Abstract Central serous chorioretinopathy (CSCR) is characterized by serous detachment of the neurosensory retina at the posterior pole with or without focal pigment epithelial detachment and altered retinal pigment epithelium. In most cases, treatment helps restore the vision, but no treatment could maximize the final visual gain. In Ayurveda, visual-related conditions are included in the Drishtigata Roga (diseases causing visual disturbance). CSCR based on clinical presentation can be categorized under Dhumadarshi. A 42-year-old female came to the outpatient department of Shalakya tantra with the complaint of dimness in vision in the left eye (OS: oculus sinister) for 2 days, along with a black spot in the center of her vision while walking. On examination, unaided distant visual acuity was 6/36 in the left eye (OS) and 6/9 in the right eye (OD: oculus dexter). On optical coherence tomography examination, it was diagnosed as a case of CSCR. Interventions included in this study were on an outpatient basis with the potential action of Shothahara (anti-inflammatory), Vatanulomana (pacification of obstructed Vata), Medhya (intellect enhancer), and Drishtiprasadana (enhancing eyesight). At the end of the consultation, the vision was restated to normal, and the accumulation of subretinal fluid was completely resolved. In conclusion, Ayurvedic intervention can aid in accelerating visual restoration and reducing accumulation of subretinal fluid.

Multimodal Retinal Imaging Reveals New Pathogenic Insights in Central Areolar Choroidal Dystrophy: A Case Series.

To describe novel imaging findings in a family affected by central areolar choroidal dystrophy (CACD). Case series with multimodal retinal imaging assessment. A 19-year-old asymptomatic woman was referred for bilateral macular defects of the retinal pigment epithelium (RPE). Blue-light autofluorescence (BAF) of her right eye revealed a speckled pattern in the macular area with a ring of decreased autofluorescence using near-infrared autofluorescence (NIR-AF). Multimodal assessment of her left eye disclosed a single parafoveal spot of decreased pigmentation that was clearly visible as hyper-autofluorescent using BAF and as hypo-autofluorescent using NIR-AF. Optical coherence tomography angiography (OCT-A) revealed several tiny areas of flow voids in correspondence of the RPE alterations of both eyes.Three family members were recently diagnosed with presumed age-related macular degeneration and demonstrated well-demarcated areas of RPE atrophy surrounded by yellowish deposits and a hypo-pigmented halo.Next-generation genetic analysis for inherited macular dystrophies was performed on the index case and the affected family members and revealed a p.Arg172Gln missense mutation in PRPH2 gene, leading to the diagnosis of CACD. Multimodal imaging can reveal new pathogenic insights in CACD. Of notice, NIR-AF and OCT-A are able to detect RPE hypopigmentation and choriocapillaris rarefaction, respectively, since the earliest stages of the disease.

MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR?

To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy. Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed. Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy. Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy .

Peripheral Retinal Involvement in Extensive Macular Atrophy with Pseudodrusen-Like Deposits

To describe the alterations of the peripheral retina in extensive macular atrophy with pseudodrusen-like deposits (EMAP) by means of ultrawidefield fundus photography (UWFFP) and ultrawidefield fundus autofluorescence (UWF-FAF). Prospective, observational case series. Twenty-three patients affected by EMAP. Each patient underwent best-corrected visual acuity (BCVA) measurement, UWFFP, and UWF-FAF. The area of macular atrophy, as well as the pseudodrusen-like deposits and peripheral degeneration, were assessed using UWF images, at baseline and over the follow-up. The assessment of the clinical patterns of both pseudodrusen-like deposits and peripheral retinal degeneration. Secondary outcomes included assessing macular atrophy by means of UWFFP and UWF-FAF, and tracking progression over the follow-up. Twenty-three patients (46 eyes) were included, of whom 14 (60%) were female. Mean age was 59.0 ± 5 years. Mean BCVA at baseline was 0.4 ± 0.4, declining at a mean rate of 0.13 ± 0.21 logarithm of the minimum angle of resolution/year. Macular atrophy at baseline was 18.8 ± 14.2 mm2 on UWF-FAF, enlarging at a rate of 0.46 ± 0.28 mm/year, after the square root transformation. Pseudodrusen-like deposits were present in all cases at baseline, and their detection decreased over the follow-up. Three main types of peripheral degeneration were identified: retinal pigment epithelium alterations, pavingstone-like changes, and pigmented chorioretinal atrophy. Peripheral degeneration progressed in 29 eyes (63.0%), at a median rate of 0.7 (interquartile range, 0.4-1.2) sectors/year. Extensive macular atrophy with pseudodrusen-like deposits is a complex disease involving not only the macula, but also the midperiphery and the periphery of the retina. Proprietary or commercial disclosure may be found after the references.

Role of HIF1α and HIF2α in Cre Recombinase–Induced Retinal Pigment Epithelium Pathology and Its Secondary Effect on Choroidal Neovascularization

CreTrp1 mice are widely used for conditional retinal pigment epithelium (RPE) gene function studies. Like other Cre/LoxP models, phenotypes in CreTrp1 mice can be affected by Cre-mediated cellular toxicity, leading to RPE dysfunction, altered morphology and atrophy, activation of innate immunity, and consequent impairment of photoreceptor function. These effects are common among the age-related alterations of RPE that feature in early/intermediate forms of age-related macular degeneration. This article characterizes Cre-mediated pathology in the CreTrp1 line to elucidate the impact of RPE degeneration on both developmental and pathologic choroidal neovascularization. Nonredundant roles of the two major components of the hypoxia-inducible factor (HIF) family of transcription regulators, HIF1α and HIF2α, were identified. Genetic ablation of Hif1a protected against Cre-induced degeneration of RPE and choroid, whereas ablation of Hif2a exacerbated this degeneration. Furthermore, HIF1α deficiency protected CreTrp1 mice against laser-induced choroidal neovascularization, whereas HIF2α deficiency exacerbated the phenotype. Cre-mediated degeneration of the RPE in CreTrp1 mice offers an opportunity to investigate the impact of hypoxia signaling in the context of RPE degeneration. These findings indicate that HIF1α promotes Cre recombinase-mediated RPE degeneration and laser-induced choroidal neovascularization, whereas HIF2α is protective.

Hyperreflective material in patients with non-neovascular pachychoroid disease

BackgroundThis study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients.MethodsA retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes.ResultsAll cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period.ConclusionThere are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

Fundus autofluorescence abnormalities can predict fluorescein angiography abnormalities in patients with chronic central serous chorioretinopathy.

This study is to assess the possible correlation between findings on fundus autofluorescence (FAF) and fluorescein angiography (FA) in patients with chronic central serous chorioretinopathy (cCSC). This multicentre retrospective cohort study included 71 cCSC patients (92 eyes) with at least 6months of follow-up, who had a FAF-FA imaging discrepancy larger than 0.5 optic disc diameters in size in the corresponding areas of hyperfluorescent abnormalities. A comparison was performed between progression in size of areas of hyperautofluorescent retinal pigment epithelium (RPE) abnormalities on FAF (HF-FAF) and the hyperfluorescent areas on FA (HF-FA) at first visit and last visit. The possible correlations were estimated between FAF-FA discrepancy and disease characteristics. The median area of HF-FAF at first visit was 7.48mm2 (1.41-27.9). The median area of HF-FA at first visit and last visit was 2.40mm2 (0.02-17.27) and 5.22mm2 (0.53-25.62), respectively. FAF-FA discrepancy was associated with follow-up duration and the area of HF-FAF at first visit. A mathematical algorithm for grading FAF-FA discrepancy in time was suggested, which predicted the enlargement of hyperfluorescent RPE abnormalities on FA in 82.6% of cases. There is a statistically significant relationship between the areas of HF-FAF and HF-FA in cCSC patients with FAF-FA imaging discrepancy at first presentation. Long-term changes in RPE alterations in cCSC on FA can be predicted based on baseline HF-FAF and follow-up duration.

Ten-year follow-up and sequential evaluation of multifocal retinal pigment epithelium abnormalities in central serous chorioretinopathy.

The study aims to analyze the 10-year outcomes in "simple" and "complex" central serous chorioretinopathy (CSCR) and to evaluate the longitudinal changes in multifocal retinal pigment epithelium (RPE) alterations. This was a retrospective, multicentric, longitudinal, observational study in patients with a diagnosis of CSCR. Visual acuity outcomes and recurrence characteristics of simple and complex were analyzed. Changes in number of foci of RPE alterations from baseline to last visit were evaluated. Out of 235 eyes screened, the study included 67 eyes of 39 patients (32 males and 7 females) with CSCR (12 simple and 55 complex CSCR). A total of 17 (29.9%) eyes had a unifocal RPE alteration, while the remaining 50 had multifocal RPE alterations at baseline. In eyes with complex CSCR, the 10-year visual acuity was significantly worse (p < 0.001), more number of eyes required treatment (p = 0.03), higher number of RPE alterations were present at baseline and last follow-up (p < 0.001 for both), and number of recurrences were higher (p < 0.001), than simple CSCR. Focal collections of RPE alterations and leakage site corresponded to mid-phase hyper-fluorescent plaques (MPHP) in all eyes. On multivariate regression analysis, a larger area of RPE alteration was associated with a worser 10-year visual acuity (p = 0.004) and complex CSCR was associated with higher number of recurrence (p = 0.005). A different course of disease progression was seen in simple and complex CSCR. An evolution in foci of RPE alterations was seen, from a simple area of MPHP, to focal RPE alterations and finally to leakage.

Assessment of Retinal Pigment Epithelium Alterations and Chorioretinal Vascular Network Analyses in Patients under Treatment with BRAF/MEK Inhibitor for Different Malignancies: A Pilot Study.

In the last two decades, an increasing number of so-called molecular-targeted therapies have become available for the treatment of patients with advanced malignancies. These drugs have included inhibitors of proteins in the MAPK pathway, such as BRAF and MEK inhibitors, which are characterized by a distinct toxicity profile. The eye is particularly susceptible to adverse effects due to MEK inhibitors, and the term MEKAR (MEK-inhibitor-associated retinopathy) indicates the presence of subretinal fluid, mimicking central serous chorioretinopathy (CSC). The pathogenesis of the retinal alterations related to MAPK pathway inhibitors is still unclear, and questions are still open. The present study aims to assess the presence of retinal pigment epithelium alterations as predictive parameters for retinal toxicity, analyzing, at the same time, the chorioretinal vascular network in patients undergoing BRAF/MEK inhibitor treatment for different malignancies.

ASSOCIATION BETWEEN CENTRAL SEROUS CHORIORETINOPATHY [CSCR] AND CORONARY HEART DISEASE [CHD] IN PATIENTS ATTENDING THE OUTPATIENT DEPARTMENT OF REGIONAL INSTITUTE OF OPHTHALMOLOGY KOLKATA: A CASE CONTROL STUDY

Introduction: Central serous chorioretinopathy [CSCR] a disease characterized by localized and serous detachments of neurosensory retina with or without focal pigment epithelial detachments[PEDs] and altered retinal pigment epithelium[RPE].The disease is usually idiopathic and often resolves spontaneously with visual recovery, although occasionally neurosensory retinal detachment persists or relapses and leads to permanent damage of the retinal pigment epithelium [RPE] and photoreceptors with subsequent visual impairment.Aims: In this Study CSCR patients and a control group were evaluated for the presence of CHD by means of Electrocardiogram [EKG], and echocardiogram and by further investigations if needed. Materials and Methods:The Institution based retrospective case control study. This Study was conducted from 12 months at Department of OPD at Regional Institute of Ophthalmology, [RIO] and Kolkata. Result: In our study, case group 25 [12.5%] patients had CHD and in control group, 12 [6.0%] patients had CHD which was statistically signicant [p=0.0248]. Conclusion: We concluded that association between Central Serous Chorioretinopathy (CSCR) and Coronary Heart Disease [CHD] was statistically signicant. CSCR had a signicantly higher CHD rate than those without CSCR, indicating that CSCR may be a potential risk factor for the development of CHD

Retinal Findings in Hospitalized COVID-19 Patients, Is Routine Ophthalmological Examination Required after Discharge? Prospective Case-Control Study.

To investigate retinal findings by comparing patients hospitalized for COVID-19 with the control group. In this prospective study, 188 eyes of 94 recovered COVID-19 patients and 108 eyes of 54 healthy participants as a control group were evaluated. Patients were divided into three groups, those with mild, moderate, and severe COVID-19. Refractometry, tonometry, optical biometry, optical coherence tomography (OCT) measurements, and complete ophthalmological examinations were performed on healthy volunteers and COVID-19 patients on average 2 weeks after discharge. Pulse O2 and vital parameters were also assessed. Primary outcomes were evaluated, such as retinal findings, and secondary outcomes as retinal thickness, choroidal thickness (CT), retinal nerve fiber layer thickness, and ganglion cell layer thickness. There was no difference between the groups in terms of demographic data, ocular biometry, and intraocular pressure (p > 0.05). Pulse O2 was lower in the study group (p < 0.001). Retinal findings were detected in 68 (36.1%) of 188 eyes in the study group and 28 (25.9%) of 108 eyes in the control group (p = 0.07). The two most common retinal findings were hypertensive retinopathy and retinal pigment epithelium alterations and/or drusen in both groups. In OCT measurements, significant thinning was observed in nasal macular thickness and superior 2 mm CT in the study group compared to the control group (p < 0.05). In patients divided into subgroups according to disease severity, no significant difference was found between the groups in any OCT parameter (p > 0.05). It has been observed that COVID-19 infection does not cause a specific and sensitive finding in the ocular tissues, especially the retina, and does not produce a reproducible measurement result. Recommending routine eye exam after COVID-19 does not seem cost-effective.

Каротиноиды в терапии возрастной макулярной дегенерации: система доставки имеет значение

Age-related macular degeneration (AMD) is one of the leading causes of low vision and blindness worldwide for people over age 60. By 2040, the number of people living with macular degeneration is expected to reach 288 million due to the exponential acceleration of population aging. A decline in visual functions caused by AMD has a significant economic impact in all countries. Besides aging, there are other multiple heterogenic risk factors associated with AMD: gender, environmental condition, lifestyle, genetic characteristics, chronic inflammatory processes in the human body, level of education, etc. It is important for the ophthalmologist to be aware of modifiable risk factors and thus to collect a comprehensive medical history, interact with patients using motivational interviewing and to involve promptly other healthcare specialists into the patient management strategy. Etiopathogenesis of AMD is still not entirely understood. However, it is known that the major pathways include age-related alterations of retinal pigment epithelium (RPE) cells, oxidative stress, dysregulated lipid metabolism, inflammation, hemodynamic changes, and neovascularization. Carotenoids lutein and zeaxanthin are natural compounds with a proven efficacy in reducing AMD progression, which have been demonstrated to act as medications for patients with early AMD stages. The micro- encapsulated formula offers such an advantage as gradual and controlled release of active substances. Keywords: age-related macular degeneration, risk factors, etiopathogenesis, carotenoids, lutein, zeaxanthin, microcapsules. For citation: Maksimov M.L., Oganezova J.G., Kanner I.D., Voznesenskaya A.A. Carotenoids in the treatment of age-related macular degeneration: a drug delivery system does matter. Russian Journal of Clinical Ophthalmology. 2023;23(1):60–65 (in Russ.). DOI: 10.32364/2311-7729-2023-23-1-60-65.

Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration; however, effective treatment is not yet available for geographical atrophy in dry age-related macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human age-related macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

Anti-Vegf therapy leads to an improvement in grade of retinal pigment epithelium alterations on single layer retinal pigment epithelium map in diabetic macular edema.

In bovine retinal pigment epithelium (RPE) cells, increased secretion of vascular endothelial growth factor (VEGF) has a positive linear association with proliferation of RPE. Spectral domain optical coherence tomography (SD-OCT) based improvement in grades of topographic retinal pigment epithelium alterations (RPE-A), were evaluated after intravitreal anti-VEGF therapy, in diabetic macular edema (DME), for the first time. A tertiary care center-based, prospective study. Forty-four consecutive patients, 40-65 years of age with type 2 diabetes mellitus (DM) with DME, were administered three doses of anti-VEGF therapy at monthly intervals. Pre- and post-intervention SD-OCT was done and central sub field thickness (CST), cube average thickness (CAT) and topographic grades of RPE-A were assessed using single layer RPE map (SL-RPE) as; Grade 0: No alterations, Grade 1: Alteration in two quadrants, Grade 2: Alteration in more than two quadrants. CST decreased from 354.2 ± 16.0 µm pre-intervention to 233.2 ± 7.9 µm post-intervention. CAT reduced from 340.6 ± 6.5 µm pre-intervention to 274.1 ± 5.1 µm post-intervention. Significant improvement in grades of RPE-A pre- v/s post-intervention were observed. (Grade 0: 0 v/s 39; Grade 1: 17 v/s 3; Grade 2: 27 v/s 2) (p < 0.001). Anti-VEGF therapy is associated with an improvement in grades of RPE-A in DME.The study was registered with the Clinical Trial Registry of India (CTRI/2019/03/018135).

Microglial activation and retinal pigment epithelium alteration in a model of focal LED‐induced phototoxicity. Neuroprotection afforded by bFGF and minocycline

AbstractPurpose: To study the microglial reaction and degeneration of the retinal pigment epithelium (RPE) and its protection with basic fibroblast growth factor (bFGF) administered alone or combined with minocycline (MC) in a model of focal light‐emitting diode (LED)‐induced phototoxicity (LIP) in mice.Methods: In dark‐adapted adult C57 mice (20–25 g), the left eye was dilated and exposed for 45 seconds to a blue LED (400 nm; 500 lux) placed 2 mm perpendicular to the corneal apex (n = 71). Mice were treated with bFGF (0.5 μg) administered alone or in combination with MC (45 mg/kg). bFGF was administered in a single intravitreal injection just after LIP and the MC was daily injected intraperitoneally, starting the day before LIP (n = 10–13 per group). Vehicle or naïve groups were used as controls (n = 6–10 each group). Retinas were immunodetected with anti‐arrestin and anti‐Iba1 antibodies to study cone outer segments (a+OS) and microglial cells (Iba1+cells) and RPEs were immunodetected with anti‐ZO1 to study RPE cells, at 3 and 7 days after LIP. The number of cones and microglial cells was studied within a pre‐fixed area (PFA) of 0.9 mm diameter at the centre of the lesion.Results: Treatment with bFGF alone or in combination with MC was effective in protecting a+OS within the PFA compared to vehicles at 7 days after LIP (p = 0.034 and p = 0.001, respectively). The combined treatment of bFGF and MC was effective in reducing the number of Iba1+cells within the PFA in the outer plexiform layer at 7 days after LIP (p = 0.0003). However, the treatments had no restorative effect on RPE cell survival or morphological integrity at 7 days after LIP (p = 0.6762).Conclusions: Administration of bFGF alone or in combination with MC increased a+OS survival and reduces Iba1+cell activation but does not reduce RPE damage.

Central serous chorioretinopathy complicated by neovascularization following panretinal photocoagulation for diabetic retinopathy

AbstractPurpose: To report a case of chronic central serous chorioretinopathy (CSCR) complicated by neovascularization following panretinal photocoagulation (PRP) for a proliferative diabetic retinopathy (DR).Methods: A 51‐year‐old man, with a medical history of diabetes mellitus and chronic CSCR presented to our department for alteration of central vision of the left eye (LE) 6 months after bilateral PRP for proliferative DR. Complete ophthalmic examination with best corrected visual acuity (BCVA) measurement, fundus photography, fundus autofluorescence (FAF), swept source optical coherence tomography (SS‐OCT), swept source optical coherence tomography angiography (SS‐OCTA) and indocyanine green angiography (ICG‐A) were performed.Results: BCVA was 20/100 in the right eye (RE) and 20/400 in the LE. Anterior segment examination was unremarkable except for a cataract in the RE. Fundoscopic examination of the LE showed multiple areas of retinal pigment epithelium (RPE) alteration and a temporal pigment epithelium detachment (PED). FAF showed multiple hypoautofluorescent lesions associated with gravitational tracks. SS‐OCT revealed a serous retinal detachment, a flat irregular PED with a double layer sign overlying a thickened choroid and dilated choroidal vessels. Mid‐phase ICGA revealed 2 discrete areas of hyperfluorescence. SS‐OCTA confirmed the presence of 2 well‐defined choroidal neovascular membranes. The patient was diagnosed with Pachychoroid Neovasculopathy (PNV). After 2 intravitreal bevacizumab injections, SS‐OCT showed complete resolution of the subretinal fluid whereas SS‐OCTA visualized a mature “dead‐tree” shaped membrane.Conclusions: This is an unusual case of chronic CSCR progressing to PNV following PRP for RD. The disruption of an active RPE pump mechanism or release of endogenous stress hormones after PRP have been suggested by some authors as possible causes of this progression. Further studies are needed to elucidate the exact pathogenesis.