Retinal Pigment Epithelium Changes Research Articles

Circumscribed choroidal hemangioma: An overview of clinical manifestation, diagnosis and management.

Circumscribed choroidal hemangioma is a benign vascular tumor which presents in middle-aged adults with progressive diminution of vision, metamorphopsia, floaters, and visual field defects. Diagnosis is based on the characteristic clinical features. It is an orange-red, usually solitary, tumor situated in the posterior pole. The visual symptoms are because of the associated subretinal fluid, cystoid macular edema, and, in long-standing cases, retinal pigment epithelium changes, subretinal fibrosis and retinoschisis. It must be distinguished from the more ominous amelanotic melanoma and choroidal metastasis. Diagnostic tools such as ultrasound, fundus fluorescein angiography, indocyanine green angiography, and optical coherence tomography are helpful in cases with diagnostic dilemma. Treatment is indicated in symptomatic cases. The management of choroidal hemangioma has evolved over the years beginning with laser photocoagulation to transpupillary thermotherapy, photodynamic therapy, plaque brachytherapy and external beam radiotherapy. No one therapeutic option holds superiority over the other. In this article, we review the epidemiology, clinical manifestations and treatment of the circumscribed variant of choroidal hemangioma.

Long term follow-up of a family with GUCY2D dominant cone dystrophy.

To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms (ERGs) and occipital pattern reversal visual evoked potentials were recorded. Two members of the same family (father and son) were identified to have the heterozygous R838C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull's eye maculopathy and temporal disc pallor. Over 13y of serial follow up visits, the bull's eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectral-domain optical coherence tomography (SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer. Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene.

Acute multifocal retinitis: a retrospective review of 35 cases

BackgroundAcute multifocal retinitis is a rare condition that has been considered to be often idiopathic. The purpose of this study was to analyze clinical features and causes of acute multifocal retinitis.ResultsThis study is a retrospective review of the charts of 35 patients with acute multifocal retinitis. Patients with three or more retinal lesions in at least one eye, with at least one lesion of less than 500 μm in size were included. All patients had complete ophthalmological examination, fundus photography, and fluorescein angiography. Twelve patients (34.3%) had optical coherence tomography. An extensive work-up was performed including a detailed comprehensive medical history, examination by an internist and an infectious disease specialist, a chest X-ray, Mantoux test, and laboratory tests for syphilis, human immunodeficiency virus, Bartonella, and Rickettsia. Of the 35 patients, 25 (71.4%) had bilateral involvement and 10 (28.6%) had unilateral involvement (total number of eyes: 60). Mean best-corrected visual acuity (BCVA) was 20/25 (range, 20/1000–20/20). Retinal lesions ranged from 3 to more than 20 in number in at least 1 eye, and from 150 to 1500 μm in size. Associated findings included mild anterior chamber inflammation in 5 eyes (8.3%), mild vitritis in 46 eyes (76.7%), optic disc swelling in 9 eyes (15%), macular star in 4 eyes (6.7%), exudative retinal detachment in 6 eyes (10%), and branch retinal artery occlusion in 6 eyes (10%). Acute multifocal retinitis was found to be caused by Rickettsia conorii infection in 20 patients (57.1%), Rickettsia typhi infection in 4 patients (11.4%), cat-scratch disease in 8 patients (22.9%), and syphilis in 1 patient (2.9%). It was idiopathic in two patients (5.7%). Retinal lesions resolved without scarring in 3 to 12 weeks in all but three eyes (5%), in which residual retinal pigment epithelial changes were noted.ConclusionRickettsial disease was the most common cause of acute multifocal retinitis. Other identified causes included cat-scratch disease and syphilis, and a very small subset of patients was diagnosed with idiopathic multifocal retinitis.

Prevalence of peripapillary choroidal neovascular membranes (PPCNV) in an elderly UK population-the Bridlington eye assessment project (BEAP): a cross-sectional study (2002-2006).

There is paucity of data on the epidemiology of peripapillary choroidal neovascularisartion (PPCNV). Our aim was to determine prevalence of PPCNV in the elderly UK population of Bridlington residents aged ≥65 years. Eyes with PPCNV in the Bridlington eye assessment project (BEAP) database of 3475 participants were analysed. PPCNV outline was drawn, its area measured, and clock-hour involvement of disc circumference recorded. Location and shortest distance from the lesion edge to fovea were recorded. Masked grading for age-related maculopathy (ARM)/reticular pseudodrusen (RPD) within the ETDRS grid was assigned for each eye using a modified Rotterdam scale. Peripapillary retinal pigment epithelial (RPE) changes/drusen were recorded. Visual acuity (VA) and demographic details analysed separately were merged with grading data. PPCNV were identified in ten subjects, and were bilateral in two (20%), a population prevalence of 0.29%, and 0.06% bilaterality. Gender-specific prevalence were 0.36% and 0.19% for females and males, respectively. Age ranged from 66 to 85 years [mean 76.3 (SD 6.4)]. PPCNV were located nasal to disc in 41.7%, measuring 0.46-7.93 mm2 [mean 2.81 mm2 (SD 2.82)]. All PPCNV eyes had peripapillary RPE changes. One subject had no ARM, 1 angioid streaks, and 30% RPD. No direct foveal involvement, or reduced VA attributable to PPCNV was observed. PPCNV were infrequent in this population, more common in females, and often located nasal to the disc, without foveal extension. Peripapillary degenerative changes were universal, and strong association with ARM was observed in eyes with PPCNV. Typically, PPCNV were asymptomatic with VA preservation.

Microtubule-Associated Protein 1 Light Chain 3B, (LC3B) Is Necessary to Maintain Lipid-Mediated Homeostasis in the Retinal Pigment Epithelium.

Like other neurons, retinal cells utilize autophagic pathways to maintain cell homeostasis. The mammalian retina relies on heterophagy and selective autophagy to efficiently degrade and metabolize ingested lipids with disruption in autophagy associated degradation contributing to age related retinal disorders. The retinal pigment epithelium (RPE) supports photoreceptor cell renewal by daily phagocytosis of shed photoreceptor outer segments (OS). The daily ingestion of these lipid-rich OS imposes a constant degradative burden on these terminally differentiated cells. These cells rely on Microtubule-Associated Protein 1 Light Chain 3 (LC3) family of proteins for phagocytic clearance of the ingested OS. The LC3 family comprises of three highly homologous members, MAP1LC3A (LC3A), MAP1LC3B (LC3B), and MAP1LC3C (LC3C). The purpose of this study was to determine whether the LC3B isoform plays a specific role in maintaining RPE lipid homeostasis. We examined the RPE and retina of the LC3B-/- mouse as a function of age using in vivo ocular imaging and electroretinography coupled with ex vivo, lipidomic analyses of lipid mediators, assessment of bisretinoids as well as imaging of lipid aggregates. Deletion of LC3B resulted in defects within the RPE including increased phagosome accumulation, decreased fatty acid oxidation and a subsequent increase in RPE and sub-RPE lipid deposits. Age-dependent RPE changes included elevated levels of oxidized cholesterol, deposition of 4-HNE lipid peroxidation products, bisretinoid lipofuscin accumulation, and subretinal migration of microglia, collectively likely contributing to loss of retinal function. These observations are consistent with a critical role for LC3B-dependent processes in the maintenance of normal lipid homeostasis in the aging RPE, and suggest that LC3 isoform specific disruption in autophagic processes contribute to AMD-like pathogenesis.

Central Serous Chorioretinopathy from the Point of View of OCT-Angiography. Part 1. Chorioretinal Blood Flow Changes

Numerous recent studies indicate that the key mechanism for the development of central serous chorioretinopathy (CSR) is damage to retinal pigment epithelium (RPE). At the same time, the reports appeared in recent years indicate that an equally important link in pathogenesis is the disturbances of the choroidal blood flow. Thus, the introduction into clinical practice of optical coherence tomography in the angiography (OCTA) mode made it possible to visualize the retinal and choroidal vessels taking into account their segmentation, which opens up prospects for studying chorioretinal blood flow in the CSR.Purpose:to reveal the regularities of the change in the choroidal blood flow in patients with SCR according to the OCTA data, to assess their informativeness and role in the pathogenesis of the disease.Patients and methods:26 patients with SCR aged 35–54 years were examined. To assess the chorioretinal blood flow, optical coherence tomography of the retina is included in the angiography mode in the scope of the diagnostic examination.Results and discussion:It has been revealed that the number of large vessels in the immediate vicinity of the RPE is increasing in SCR, i.e. the vessels move towards the retina in the direction of the least resistance. Disturbance of the hierarchy of the vasculature is an important fact, allowing to speak about pronounced hemodynamic disorders. Disturbance of the topography of large-caliber vessels is accompanied by the formation of a characteristic vascular pattern. The revealed predominance of the reticular pattern of large vessels in patients with CSR is more likely due to the presence of a significant number of bifurcations and anastomoses, as well as an increase in the proportion of crossed vessels. This may be accompanied by an increase in total vascular resistance. Consequently, the hydraulic resistance can increase at these sites, a turbulent blood flow occurs and the permeability of the vascular wall increases. Correspondence between changes in RPE and choriocapillaries was established. Taking into account that the RPE detachments from 450 to 780 (on average 515 ± 72.3) μm, revealed in the projection of the altered choriocapillaries, have comparable sizes with the value of one vascular lobe (515 × 450) μm, one can speak of a local lesion of choriocapillaries and RPE within one arteriocentric lobules.Conclusions:The revealed changes in regional blood flow are progressive and can be used as classification and prognostic criteria for choroidal dysfunction.

Significant Association Between Variant in SGCD and Age-Related Macular Degeneration.

CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes—for instance, in the dystrophin-associated protein complex—might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4–5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06–3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03–3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02–0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities.

Incontinentia pigmenti-associated ocular anomalies of paediatric incontinentia pigmenti patients in China.

To characterize ocular manifestations in a cohort of paediatric patients with incontinentia pigmenti (IP) and to define the guidelines for grading of IP-associated retinopathy (IPR). This retrospective review was performed on patients under the age of 18years with a diagnosis of IP. Data included demographics, medical history, ocular examination, and accessory examination. Ocular and systemic physical examinations of the parents were carried out to determine the familial history. Sixty-one children (58 females and three males) with median age of 3.7months were observed consecutively. The median follow-up duration was 13.4months (range: 6.5-75.0months). A total of 47 patients had various ocular anomalies. Among them, 28 patients had bilateral ocular anomalies and 19 had unilateral anomalies. Vitreoretinal changes were noted in 73 of 122 eyes, including eight eyes with retinal pigment epithelium changes only (Stage 1), 22 eyes with retinal vascular abnormalities (Stage 2), five eyes with epiretinal membranes or fibrotic hyperplasia combined with avascularized zones (Stage 3), six eyes with retinal neovascularization (Stage 3), one eye with vitreous haemorrhage (Stage 3), 10 eyes with partial retinal detachment (RD) (Stage 4a), 15 eyes with total RD (Stage 4b) and eight eyes with phthisis bulbi and secondary glaucoma (Stage 5). Various vitreoretinal manifestations can be found in paediatric patients with IP and classified into five stages, which are characterized by retinal vasculopathy.

A convenient protocol for establishing a human cell culture model of the outer retina.

The retinal pigment epithelium (RPE) plays a key role in the pathogenesis of several blinding retinopathies. Alterations to RPE structure and function are reported in Age-related Macular Degeneration, Stargardt and Best disease as well as pattern dystrophies. However, the precise role of RPE cells in disease aetiology remains incompletely understood. Many studies into RPE pathobiology have utilised animal models, which only recapitulate limited disease features. Some studies are also difficult to carry out in animals as the ocular space remains largely inaccessible to powerful microscopes. In contrast, in-vitro models provide an attractive alternative to investigating pathogenic RPE changes associated with age and disease. In this article we describe the step-by-step approach required to establish an experimentally versatile in-vitro culture model of the outer retina incorporating the RPE monolayer and supportive Bruch's membrane (BrM). We show that confluent monolayers of the spontaneously arisen human ARPE-19 cell-line cultured under optimal conditions reproduce key features of native RPE. These models can be used to study dynamic, intracellular and extracellular pathogenic changes using the latest developments in microscopy and imaging technology. We also discuss how RPE cells from human foetal and stem-cell derived sources can be incorporated alongside sophisticated BrM substitutes to replicate the aged/diseased outer retina in a dish. The work presented here will enable users to rapidly establish a realistic in-vitro model of the outer retina that is amenable to a high degree of experimental manipulation which will also serve as an attractive alternative to using animals. This in-vitro model therefore has the benefit of achieving the 3Rs objective of reducing and replacing the use of animals in research. As well as recapitulating salient structural and physiological features of native RPE, other advantages of this model include its simplicity, rapid set-up time and unlimited scope for detailed single-cell resolution and matrix studies.

FIVE-YEAR FOLLOW-UP AFTER EPIRETINAL MEMBRANE SURGERY: A Single-Center Experience.

To evaluate the rate of epiretinal membrane (ERM) recurrence in eyes that underwent ERM peeling surgery at least 5 years earlier. Retrospective interventional case series study of 37 patients (15 women and 22 men; mean age, 70 ± 7.6 years) operated on for ERM removal with a follow-up of at least 5 years. The patients underwent testing for visual acuity, an ophthalmic examination, and optical coherence tomography imaging, all of which were assessed preoperatively, postoperatively, and at the 5-year follow-up. Visual acuity significantly improved at 1 year after peeling compared with baseline (P = 0.045), and the improved results were maintained at 5 years (P = 0.804) 0.766 logarithm of the minimum angle of resolution (Snellen 6/35). The central macular thickness decreased significantly at the 1-year follow-up compared with baseline and continued to decrease as measured at the 5-year follow-up (P = 0.04). At 5 years, the ERM recurrence rate reached 58% (28% extrafoveal). Photoreceptor atrophy and retinal pigment epithelium changes correlated with diabetes mellitus (P = 0.028). The recurrence rate of ERM after peeling surgery was reported as being around 5% to 12%. It was 58% in the current study. Because the recurrent ERM is generally mild, visual acuity was unaffected.

Esculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Death

ABSTRACTPurpose: Age-related macular degeneration (AMD) is the most common cause of visual loss. The dry AMD is characterized by retinal pigment epithelium (RPE) death and changes in AMD lead to severe loss of vision. Coumarin-derived esculetin has a number of therapeutic and pharmacological effects such as anti-inflammatory and antioxidant with various mechanisms. The purpose of this study was to investigate the effects of esculetin treatment on lipopolysaccharide (LPS)-induced inflammation, oxidative stress, and cell survival.Material and methods: Human RPE cells (ARPE-19) were incubated for 24–72 h with 5 μg/ml LPS to induce inflammation and oxidative stress. Esculetin (5 μM) was used to protect the cells from LPS-induced damage. The cell viability was evaluated by quantitative 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Interleukin 6 (IL-6), IL-12, and vascular endothelial growth factor (VEGF) levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1β, tumor necrosis factor receptor (TNFR), TNF-related apoptosis-inducing ligand (TRAIL), catalase, glutathione peroxidase (GPx), superoxide dismutase 1 (CuZnSOD) and SOD2 (MnSOD) mRNA expressions were analyzed by RT-quantitative polymerase chain reaction. Apoptosis was monitored by cell-based cytometer. NF-kappa B (NF-κB) p65/RelA levels were determined by ELISA, and NF-κB protein expression and extracellular signal-regulated kinase (ERK1/2) phosphorylation were evaluated by Western blot analysis.Results: Esculetin treatment significantly suppressed LPS-induced cell death mediated by apoptosis and necrosis in a concentration-dependent manner. While LPS caused significant inflammation with cytokine increase in cells, esculetin reduced the expression of LPS-induced cytokines, VEGF, TNFR, and TRAIL. Furthermore, exposure to LPS increased the expression of GPx and mitochondrial MnSOD, leading to oxidative stress in the cells. Esculetin treatment attenuated phosphorylation of ERK1/2 and NF-κB expression mediated by LPS.Conclusions: These results suggest that esculetin may be an alternative treatment option for endotoxin-induced inflammation and oxidative stress, which therefore may inhibit the development of LPS-mediated AMD.

Amblyopia or Pathology? Diffuse Unilateral Subacute Neuroretinitis in a Pediatric Patient

Background: Diffuse unilateral subacute neuroretinitis (DUSN) is a retinal disorder cause by a subretinal nematode. The disorder tends to affect children and young adults. It is characterized by unilateral retinal pigment epithelium changes, vitritis, retinal vessel narrowing and, in advanced stages, optic atrophy. Patients are generally asymptomatic or report a painless loss of vision. It has been described in the United States as well as Latin America, Asia and Europe. Case Report: A 9 year old female, recently adopted from the Ukraine, presented for an eye exam after failing a vision screening. Uncorrected visual acuity was 20/20 OD, 20/30 OS with hyperopia OS>OD. A dilated examination revealed pigment epithelial changes in the macula OS only. Examination by a retinal specialist included ocular coherence topography and a fluorescein angiography. Blood work and stool samples were normal. A diagnosis of DUSN was made and laser photocoagulation was performed around the suspected worm. The patient tolerated the procedure well. After treatment, and with her eyeglasses, visual acuity was 20/25 OS. Conclusion: Diffuse unilateral subacute neuroretinitis (DUSN) is a condition that can be detected on a routine exam in asymptomatic patients. Recognition of the condition and prompt treatment is important to help delay disease progression and preserve visual acuity.

THE IMPORTANCE OF THE PERIPHERAL RETINA IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY.

This research investigated the peripheral retinas of patients with central serous chorioretinopathy (CSCR). Sixty patients with CSCR and 60 age- and gender-matched controls were included in this prospective cross-sectional study. All 120 participants underwent ocular examinations and peripheral retinal evaluations using a Goldmann three-mirror lens. The examinations demonstrated peripheral retinal degeneration, atrophic or hyperplastic retinal pigment epithelial changes, and retinal breaks. The peripheral retinal degeneration rate was 39% in the CSCR group and 15% in the control group, and the CSCR group reported significantly more lattice degeneration than the control group (22 vs. 3%) (P = 0.004, odds ratio = 1.97, confidence interval = 0.68-5.65 and P = 0.002, odds ratio = 4.55, confidence interval = 0.77-26.83, respectively). Symptomatic U-shaped retinal breaks were found in three eyes (5%) in the CSCR group, and the rate of peripheral retinal degeneration was higher in the patients with chronic CSCR (vs. acute CSCR). However, this difference was not significant (P = 0.244). This study showed that peripheral retinal abnormalities, particularly lattice degeneration, are more common in patients with CSCR. Therefore, the authors recommend regular retinal examinations, with the inclusion of peripheral retinal assessments, for patients with CSCR.

Retinal pigment epithelium changes in Kartagener syndrome

PurposeWe present the first case in the literature of a patient with Kartagener syndrome and ocular findings of nonexudative age-related macular degeneration. ObservationsA 55-year-old woman with Kartagener syndrome and chronic angle closure glaucoma presented for evaluation of the retina. Optos ultra-widefield imaging of the fundus showed glaucomatous cupping, drusen, and retinal pigment epithelium changes within the macular region. Humphrey visual field testing confirmed glaucomatous changes. Drusenoid pigment epithelial detachments were observed bilaterally with optical coherence tomography. Conclusions and importanceWe hypothesize that in addition to the lungs, spermatozoa and the Fallopian tubes, the retinal pigment epithelium may also be affected by ciliary dysfunction in individuals with Kartagener syndrome. Given recent advances in our knowledge of retinal ciliopathies, further studies are needed to understand how ciliary dysfunction affects the retina in Kartagener syndrome.

RPE morphometry in geographic atrophy due to AMD

The geographic atrophy (GA) junctional zone includes changes in retinal pigment epithelium (RPE) and Bruch's membrane complex that are still difficult to interpret even with clinical high-resolution imaging technologies. We measured and evaluated degenerative RPE cell changes in histological sections of GA eyes. In this study seven GA eyes were evaluated by light microscopy. In three eye sections, zones of typical RPE alterations were graded (0= normal; 1= irregular cells but intact layer; 2= rounded, enlarged, and/or heaped cells; 3= migrating cells in retina; 4= RPE absent). In each graded zone, we measured and analyzed A)the total height of the RPE cell layer, B)the height of individual RPE cells and C)the height of basal deposits. From the outer macula towards the central RPE atrophic area the RPE passed almost steadily upward through grades of increased pathology. A)Zone2 exhibited highly variable total RPE height (16.9± 5.6 µm) with hypertrophic and heaped cells next to atrophic ones. In comparison, zone0 and zone1 showed less variability and aregular total RPE height (10.9± 2.6 µm). B)In zone2 the size of altered RPE cells varied widely (12.4± 5.2 µm, min.5.1, max. 27.5). All detected migrating RPE cells were hypertrophic. C)In zone0 basal deposits were found sporadically. With progressing RPE alterations, basal deposits became progressively continuous and thicker and reached aconsiderable height at the atrophic zone (9.5± 4.3 µm). Our measurements confirmed that degenerative RPE phenomena, particularly of degeneration grade2/3 close to the actual RPE atrophy zone, are often large enough to be visualized in detail with already available modern imaging technologies (e. g. SD-OCT).

Morphogenesis of choroidal melanomas in OCT imaging

To specify clinicomorphologic correlations between OCT signs related to CM and its pathomorphological state as described in literature. The study included 33 patients with predominantly small CM who were examined with EDI-OCT. The following surface profiles were revealed: small and medium sized CM with even and uneven surface and with a plateau on the top; medium sized CM with flattened edge. Bruch's membrane (BM) had folds along the tumor edge in medium and big CM. In mushroom-shaped CM, extended defective areas could be observed. Increase of optical density in the inner parts of choroidal complex were seen over time. In CM of 2.9 mm and less, cavities were observed in the middle layers of choroid in the tumor area. In roughly half of the cases, vascular distention was seen in choroid in the tumor periphery. Changes of retinal pigment epithelium (RPE) included its thickening and presence of hyperreflective foci. In CM with prominence of more than 2.17 mm at the top, the changes included the formation of a 'single unitary block' at the level of BM/RPE and neurosensory retinal layers. Intraretinal cysts could be seen on top of the tumor at the level of outer retinal layers in CM with prominence of more than 1.5 mm. Comparison of OCT images of CM with various biometric parameters with literature data on pathomorphological changes helped specify early pathomorphological symptoms in perifocal choroid (a feature of initial CM) and highly dynamic phasing of secondary changes in the retina.

Opposite Roles of MerTK Ligands Gas6 and Protein S During Retinal Phagocytosis.

MerTK is required for photoreceptor outer segment (POS) phagocytosis by retinal pigment epithelial (RPE) cells, a diurnal function essential for vision maintenance. In vivo, MerTK is stimulated at the time of the phagocytic peak through an intracellular signaling pathway. However, MerTK ligands Gas6 and Protein S are expressed in both RPE cells and photoreceptors, and at least one of themrequired for phagocytosis to occur. Still, their exact rolein the retina was not clear until recently. This review combines results from different studies to shed the light on a tissue-specific regulation of MerTK function by its ligands. Indeed, with opposite effects on RPE phagocytosis and changes in their expression levels around the time of POS uptake, Gas6 and Protein S may contribute to the tight control of the acute phagocytic peak in the retina.

Novel grid combined with peripheral distortion correction for ultra-widefield image grading of age-related macular degeneration.

PurposeEyes with age-related macular degeneration (AMD) often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF) imaging.MethodsThis is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images.ResultsPeripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD.ConclusionWe present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation for the exploration of peripheral retinal pathology associated with AMD.

Comparative analysis of autofluorescence and OCT angiography in Stargardt disease

AimsTo characterise the vasculature of the retina in patients with Stargardt disease (STGD) using optical coherence tomography angiography (OCTA) and to compare these functional findings with fundus autofluorescence (FAF) imaging.MethodsThis...

Cuticular Drusen: Clinical Phenotypes and Natural History Defined Using Multimodal Imaging

To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen. Retrospective, observational cohort study and experimental laboratory study. Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n= 2), soft drusen (n= 1), and hard drusen (n= 1). We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy. Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes. The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P < 0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P< 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen. Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticulardrusen phenotype may confer a unique risk for the development of GA and neovascularization.