Retinal Pigment Epithelium Abnormalities 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.

Basal Linear Deposit: Normal Physiological Ageing or a Defining Lesion of Age-Related Macular Degeneration?

Objective: To determine if basal linear deposit (BLinD) is a specific lesion of age-related macular degeneration (AMD). Methods: The cohort was selected from a clinically and histopathologically validated archive (Sarks Archive) and consisted of 10 normal eyes (age 55-80 years) without any macular basal laminar deposit (BLamD) (Sarks Group I) and 16 normal aged eyes (age 57-88 years) with patchy BLamD (Sarks Group II). Only eyes with in vivo fundus assessment and corresponding high-resolution transmission electron microscopy (TEM) micrographs of the macula were included. Semithin sections and fellow-eye paraffin sections were additionally examined. BLinD was defined as a diffuse layer of electron-lucent vesicles external to the retinal pigment epithelium (RPE) basement membrane by TEM and was graded as follows: (i) Grade 0, absence of a continuous layer; (ii) Grade 1, a continuous layer up to three times the thickness of the RPE basement membrane (0.9 µm); (iii) Grade 2, a continuous layer greater than 0.9 µm. Bruch's membrane (BrM) hyalinisation and RPE abnormalities were determined by light microscopic examination of corresponding semithin and paraffin sections. Results: BLinD was identified in both normal (30%) and normal aged (62.5%) eyes. BLinD was thicker in normal aged eyes (p = 0.045; 95% CI 0.04-3.4). BLinD thickness positively correlated with both the degree of BrM hyalinisation (p = 0.049; 95% CI 0.05-2.69) and increasing microscopic RPE abnormalities (p = 0.022; 95% CI 0.188-2.422). RPE abnormalities were more likely to be observed in eyes with increased BrM hyalinisation (p = 0.044; 95% CI 0.61-4.319). Conclusions: BLinD is most likely an age-related deposit rather than a specific lesion of AMD. Its accumulation is associated with increasing BrM hyalinisation and microscopic RPE abnormalities, suggesting a relationship with dysregulated RPE metabolism and/or transport.

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.

Asymptomatic retinal dysfunction in a patient with alpha-methylacyl-CoA racemase deficiency.

To present a case of a young female patient with asymptomatic retinal dysfunction associated with alpha-methylacyl-CoA (AMACR) racemase deficiency. Retrospective analysis of the medical notes of a single patient. Detailed slit-lamp examination was completed by Optos colour fundus photography and enhanced depth imaging optical coherence tomography (EDI-OCT). Genetic testing was conducted to establish the diagnosis, and the patient was also referred to the Department of Neurology for further assessment. Dilated fundoscopy and ophthalmic imaging revealed bilateral retinal pigment epithelium abnormalities that could be associated with a genetic retinal disorder. Indeed, genetic testing showed that this lady was homozygous for AMACR (OMIM 604489; Gene ID 23600) variant NM 014324.6: c.154T>C; p.(Ser52Pro). She had no detectable neurological deficit. AMACR deficiency is a rare genetic condition that can potentially contribute to retinal dystrophy through various mechanisms. Additionally, it may lead to a wide spectrum of systemic signs and symptoms. Interestingly, in contrast to other reported studies, our patient was completely asymptomatic, with no evidence of systemic disorders.

Retinal Layer and Choroidal Changes in Deep and Scuba Divers: Evidence of Pachychoroid Spectrum‐Like Findings

Purpose: Diving is an intense physical activity under hyperbaric and hyperoxic conditions. The aim of this study is to evaluate the long‐term effects of diving on the thicknesses of retinal layers and retinal anatomy in professional deep and scuba divers.Methods: The study included 52 eyes of deep divers who dive to depths of more than 130 feet (ft), 49 eyes of scuba divers who dive up to 130 ft, and 66 eyes of the control group, consisting of nondiving but regularly exercising males. Measurements of macular retinal layer thicknesses, peripapillary nerve fiber layer thickness, subfoveal choroidal thickness, and peripheral retinal examinations with scleral indentation were performed and statistically compared between the groups.Results: The mean diving duration was 455.00 ± 318.88 h in deep divers and 451.67 ± 281.10 h in scuba divers. The retinal pigment epithelium (RPE) was statistically significantly thicker in deep divers than in scuba divers and the control group on the 3 mm ring of the Early Treatment Diabetic Retinopathy Study grid. Subfoveal choroidal thickness was significantly thicker in deep divers than in scuba divers (p < 0.05). RPE abnormalities showed a significant increase in both the deep and scuba diver groups (p = 0.01).Conclusion: An increased thickening of the subfoveal choroid and RPE, resembling pachychoroid pigment epitheliopathy, was detected in deep divers over a long‐term duration.

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration.

The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The inadequate knowledge of RPE pathology is hindered by a lack of patient RPE datasets, especially at the single-cell resolution. In this study, we delved into a large-scale single-cell resource of AMD donors in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both in vivo and in vitro models revealed that carboxypeptidase X, M14 family member 2 (CPXM2) was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrate that CPXM2 plays a crucial role in regulating atrophic AMD and may serve as a potential therapeutic target for atrophic AMD.

Optical Coherence Tomography Features of Macular Hyperpigmented Lesions without Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration

Purpose To evaluate the optical coherence tomography (OCT) features of hyperpigmented lesions in the absence of intraretinal hyperreflective foci (IHRF) on OCT in eyes with age-related macular degeneration (AMD). Methods We retrospectively analyzed OCT images of eyes with intermediate AMD (iAMD) and macular hyperpigmentation (HP) on color fundus photograph (CFP) but without IHRF on OCT in the corresponding location. The most prominent or definite HP was selected for analysis. The infrared reflectance (IR) image registered with the CFP, and the location corresponding to the HP lesion were defined on the IR image. The location of the HP on the corresponding OCT B-scan was assessed for retinal pigment epithelium (RPE) elevation, acquired vitelliform lesion (AVL), abnormal retinal pigment epithelium + basal lamina (RPE + BL) band reflectivity, RPE + BL band thickening, as well as interdigitation zone (IZ), ellipsoid zone (EZ) and external limiting membrane (ELM) disruption. Results 49 eyes (39 patients) were included in this study. Forty-six (94%) of the hyperpigmented lesions showed a thickened RPE + BL band. RPE + BL band reflectivity was increased in 37 (76%) of the lesions. RPE + BL band thickening, however, was not correlated with RPE + BL band reflectivity (p-value = 0.31). Either thickening or hyperreflectivity of the RPE + BL band was present in all cases. Twenty (41%) lesions had evidence of ELM disruption, 42 (86%) demonstrated EZ disruption and 48 (98%) had IZ disruption. Five (10%) HPs demonstrated AVL. Among cases with RPE elevation (15 cases, 31%), 10 were classified as drusen, 2 as drusenoid PEDs, and 3 as fibrovascular PEDs. Conclusions Thickening and/or hyperreflectivity of the RPE + BL band commonly correspond to regions of macular hyperpigmentation without IHRF in eyes with iAMD.

Conditional loss of Ube3d in the retinal pigment epithelium accelerates age-associated alterations in the retina of mice.

Several studies have suggested a correlation between the ubiquitin-proteasome system (UPS) and age-related macular degeneration (AMD), with its phenotypic severity ranging from mild visual impairment to blindness, but the mechanism for UPS dysfunction contributing to disease progression is unclear. In this study, we investigated the role of ubiquitin protein ligase E3D (UBE3D) in aging and degeneration in mouse retina. Conditional knockout of Ube3d in the retinal pigment epithelium (RPE) of mice led to progressive and irregular fundus lesions, attenuation of the retinal vascular system, and age-associated deterioration of rod and cone responses. Simultaneously, RPE-specific Ube3d knockout mice also presented morphological changes similar to the histopathological characteristics of human AMD, in which a defective UPS led to RPE abnormalities such as phagocytosis or degradation of metabolites, the interaction with photoreceptor outer segment, and the transport of nutrients or waste products with choroidal capillaries via Bruch's membrane. Moreover, conditional loss of Ube3d resulted in aberrant molecular characterizations associated with the autophagy-lysosomal pathway, oxidative stress damage, and cell-cycle regulation, which are implicated in AMD pathology. Thus, our findings strengthen and expand the impact of UPS dysfunction on retinal pathophysiology during aging, indicating that genetic Ube3d deficiency in the RPE could lead to the abnormal formation of pigment deposits and secondary fundus alterations. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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.

Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes

Choriocapillaris flow deficits detected on optical coherence tomography angiographs were retrospectively analyzed. In 38 age-related macular degeneration (AMD) fellow eyes, without fundus findings (26 men, 71.7 ± 1.9 years old), and 22 control eyes (11 men, 69.4 ± 1.8), the choriocapillaris flow area (CCFA) ratio and coefficient of variation (CV) of the CCFA ratio (which represented the heterogeneity of the ratio), negatively and positively correlated with age (all p < 0.01), respectively. Moreover, the respective mean values were lower (p = 0.0031) and greater (p = 0.002) in AMD fellow eyes than in the control eyes. The high-risk condition of AMD fellow eyes was defined by a CCFA ratio <58.5%, and the CV of the CCFA ratio ≥0.165 (odds ratio (OR), 5.408; 95% confidence interval (CI): 1.117-21.118, p = 0.035, after adjusting for age and sex) was related to the presence of fundus autofluorescence abnormality (OR, 16.440; 95% CI, 1.262-214.240; p = 0.033) and asymmetrically dilated choroidal large vasculature (OR, 4.176; 95% CI, 1.057-16.503; p = 0.042), after adjusting for age and sex. The presence of fundus autofluorescence abnormality indicated a retinal pigment epithelium (RPE) abnormality. The RPE volume was reduced in the latter eye group, particularly in the thinner choroidal vasculature. In addition to aging, RPE abnormality and choroidal large vascular flow imbalances were associated with exacerbated heterogeneous choriocapillaris flow deficits in AMD fellow eyes without macular neovascularization.

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.

Differentiating drusen and drusenoid deposits subtypes on multimodal imaging and risk of advanced age-related macular degeneration

Drusen are extracellular material considered a precursor lesion to advanced age-related macular degeneration (AMD), located either on the retinal pigment epithelium (RPE) or the sub-RPE; they contain various proteins associated with inflammation and lipids. Previous studies suggest that the lifecycle of drusen varies depending on drusen type and size. In general, conventional drusen grow and aggregate/coalesce in the first stage, and in the second stage, they regress with or without showing RPE atrophy. The risk of advanced AMD also varies depending on the drusen and drusenoid deposit types' along with their size and RPE abnormalities. In eyes with macular neovascularization (MNV), specific drusen/drusenoid deposits are closely associated with the MNV subtype. Recently, pachychoroid-associated drusen (pachydrusen) were proposed and clinical findings regarding this entity have been accumulating, as more attention is focused on drusen as well as pachychoroid diseases. With the advance in imaging modalities, various modalities can show specific characteristics depending on drusen types. To assess the risk of advanced AMD, it is essential for physicians to have accurate clinical knowledge about each druse/drusenoid lesion and correctly evaluate its imaging characteristics using multimodal imaging. This review summarizes the latest clinical knowledge about each druse/drusenoid lesions and documents their imaging characteristics on multimodal imaging, allowing clinicians to better manage patients and stratify the risk of developing advanced AMD. The most representative cases are illustrated, which can be helpful in the differential diagnosis of drusen and drusenoid deposits.

Pigment epithelium and choroid changes in pachychoroid pigment epitheliopathy: A descriptive study

AbstractPurpose: To describe characteristic elementary lesions of retinal pigment epithelium and choroidal vascular parameters determined by swept source optical coherence tomography (SS‐OCT) and OCT‐angiography (OCT‐A) in eyes with pachychoroid pigment epitheliopathy.Methods: Twenty‐seven patients with retinal pigment epithelium (RPE) abnormalities associated to pachychoroid features, with no history or findings indicative of subretinal fluid or soft drusen were evaluated. All eyes underwent comprehensive ophthalmic examination, fundus photography, SS‐OCT and OCT‐A. After binarization of B‐scan images with ImageJ Software, the choroidal vascularity index (CVI), the choroidal vascularity proportion (CVP) and flow voids area were calculated.Results: A total of 27 eyes of 23 patients, 19 of whom were male (70.37%), with a mean age of 59.11 ± 12.76 years were enrolled in this study. We detected six different types of RPE lesions: focal disruption in ellipsoid and interdigitation zones in 18 eyes (66.66%), RPE elevation with microbreak appearance in 12 eyes (44.44%), RPE thickening in 10 eyes (37.03%), small pigment epithelium detachment in seven eyes (25.92%), RPE spike in five eyes (18.51%) and outer nuclear layer thinning in five eyes (18.51%). The subfoveal choroidal thickness (SFCT) was 399, 78 ± 88, 13 μm. The mean inner choroidal thickness was 87.18 ± 36.67 μm. The CVI was 65.28 ± 3.35%. The CVP was 59.10 ± 0.58% in the choriocapillaris and 59.69 ± 1.42% in the Haller layer. The total choriocapillaris flow void area was 39.87 ± 1.21%.Conclusions: SS‐OCT and OCT‐A are valuable diagnostic tools to characterize pigment epithelium and choroidal changes in PPE eyes.

The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy

BackgroundThis study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis.MethodsFive individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients.ResultsDespite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy.ConclusionsRPE and choroidal atrophy were found to play an important role in the development of macular caldera.

Prevalence of Age-Related Macular Degeneration in the US in 2019

Age-related macular degeneration (AMD) is a leading cause of vision loss and blindness. AMD prevalence has not been estimated for the US in over a decade and early-stage AMD prevalence estimates are scarce and inconsistently measured. To produce estimates of early- and late-stage AMD prevalence overall and by age, gender, race and ethnicity, county, and state. The study team conducted a bayesian meta-regression analysis of relevant data sources containing information on the prevalence of AMD among different population groups in the US. We included data from the American Community Survey (2019), the National Health and Nutrition Examination Survey (2005-2008), US Centers for Medicare & Medicaid Services claims for fee-for-service beneficiaries (2018), and population-based studies (2004-2016). We included all relevant data from the US Centers for Disease Control and Prevention's Vision and Eye Health Surveillance System. The prevalence of early- and late-stage AMD was estimated and stratified when possible by factors including county, age group, gender, and race and ethnicity. Data analysis occurred from June 2021 to April 2022. The prevalence of early- (defined as retinal pigment epithelium abnormalities or the presence of drusen 125 or more microns in diameter in either eye) and late-stage (defined as choroidal neovascularization and/or geographic atrophy in either eye) manifestations of AMD. This study used data from nationally representative and local population-based studies that represent the populations in which they were conducted. For 2019, we estimated that there were 18.34 million people 40 years and older (95% uncertainty interval [UI], 15.30-22.03) living with early-stage AMD, corresponding to a crude prevalence rate of 11.64% (95% UI, 9.71-13.98). We estimated there were 1.49 million people 40 years and older (95% UI, 0.97-2.15) living with late-stage AMD, corresponding to a crude prevalence rate of 0.94% (95% UI, 0.62-1.36). Prevalence rates of early- and late-stage AMD varied by demographic characteristics and geography. We estimated a higher prevalence of early-stage AMD and a similar prevalence of late-stage AMD as compared with earlier studies. State-level and county-level AMD estimates may help guide public health practice.

Retinal changes of primary vitreoretinal lymphoma after intravitreal methotrexate

BackgroundTo identify retinal changes using spectral-domain optical coherence tomography (SD-OCT) and ultra-widefield images in eyes with primary vitreoretinal lymphoma (PVRL) during intravitreal methotrexate (MTX) treatment. MethodsThis study retrospectively reviewed 111 eyes of 58 patients with vitreous cytology-proven confirmed PVRL, who received intravitreal injections of MTX.ResultsAt the initial visit, the OCT manifestations included vitreous cells (105 eyes, 94.6%), intraretinal infiltration (44 eyes,39.6%), subretinal infiltration (45 eyes, 40.5%,), retinal pigment epithelium (RPE) abnormalities (66 eyes, 59.5%), disruption of the ellipsoid zone (58 eyes, 52.3%), subretinal fluid (4 eyes, 3.6%), RPE detachment (PED) (28 eyes, 25.2%), epiretinal membrane (ERM) (8 eyes, 7.2%), macular edema (10 eyes, 9%). After therapy, tumor regression was achieved in all eyes. Between the initial presentation and regression, the vitreous cells (94.6% vs. 0%, P < 0.001), intraretinal infiltration (39.6% vs. 0%, P < 0.001), RPE abnormalities (59.5% vs.19.8%, P < 0.001), PED (25.2% vs.0%, P < 0.001), and subretinal infiltration (40.5%vs.16.2%, P < 0.001) were significantly reduced. The fundus photography findings all improved after therapy. The mean Logarithm of the Minimum Angle of Resolution (logMAR) for the best corrected visual acuity (BCVA) at presentation was 0.79 ± 0.81 (range, 0–2.9), which improved to 0.70 ± 0.97 (range, 0–2.9, P = 0.01) at the final visit.ConclusionsSD-OCT combined with ultra-widefield imaging, which can reflect retinal changes, are valuable tools for monitoring the effect of PVRL treatment.

Choroidal flame.

A 31-year-old lady came for routine refractive check-up. Her best corrected visual acuity was 6/6 in both eyes (OU). Intraocular pressure and anterior segment examination were normal in OU. Fundus examination showed clear vitreous, normal disk, retinal vasculature, and fovea. Large ill-defined areas of orange-colored choroidal lesions were noted over superonasal, nasal, and inferonasal quadrants in Right eye (OD) [Fig. 1a]. The rest of the choroidal background appeared normal. Left eye had similar areas of ill-defined orangish choroidal lesions in nasal and inferotemporal periphery [Fig. 1b].Figure 1: (a) Right eye color fundus montage showing orange-colored choroidal lesion occupying nasal half of the fundus. (b) Left eye shows similar lesion in the peripheral quadrantsWhat is Your Next Step? Look for similar pigmentary lesions over ocular adnexa or rest of the body B scan ultrasonography Fundus autofluorescence All of the above. Findings There was no significant previous systemic or ocular history. There was also no history of any topical or systemic medication use in this patient. Thorough examination ruled out cutaneous hypopigmented lesions, poliosis, or white forelock. Ocular examination revealed no evidence of past or present intraocular inflammation. Optical coherence tomography scan through the lesions was normal with no evidence of overlying retinal pigment epithelium (RPE) abnormalities. B scan ultrasonography ruled out mass lesions and revealed normal choroidal thickness throughout. The lesions remained stable in follow-up over a period of 2 years. Diagnosis Primary choroidal vitiligo. Correct Answer D. All of the above. Discussion Primary choroidal vitiligo is an uncommon benign asymptomatic lesion that presents as flat depigmentation of the choroid. It is usually associated with cutaneous vitiligo, often of the lids and periorbital region. Secondary choroidal vitiligo occurs following intraocular inflammation, particularly Vogt–Koyanagi–Harada (VKH) syndrome.[1] Choroidal hypopigmentation with uveitis, poliosis, and hyperacusis also constitutes a rare syndrome called Alezzandrini syndrome.[2] Presence of white forelock and iris hypopigmentation with typical facial features points toward Waardenburg syndrome.[3] Investigations including angiography, autofluorescence, and ultrasonography helps us rule out conditions mimicking choroidal vitiligo, including amelanotic choroidal nevus, choroidal osteoma, diffuse choroidal hemangioma, amelanotic melanomas, and chorioretinal atrophy. Usually, primary choroidal vitiligo is a nonprogressive condition and no treatment is required. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Redefining the Spectrum of Pentosan Polysulfate Retinopathy: Multimodal Imaging Findings from a Cross-Sectional Screening Study

There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity (VA) testing and multimodal imaging, we investigated the impact of PPS therapy on vision and described an expanded spectrum of imaging findings among PPS users. Cross-sectional screening study. Thirty-nine patients who were current or recent users of PPS. The participants underwent a brief eye examination and answered a comprehensive medical and ophthalmic history questionnaire. Color fundus photography, fundus autofluorescence (FAF), and spectral-domain OCT (SD-OCT) were performed. The images were evaluated by expert graders at Wisconsin Reading Center. Abnormalities were categorized as definite toxicity (DT) if seen on both FAF and SD-OCT and as questionable toxicity (QT) if seen on either FAF or SD-OCT. ETDRS and Snellen VA, the dosage and duration of PPS exposure, and the prevalence of retinal toxicity on imaging. The mean ETDRS and Snellen VA of the study cohort were 85 letters and 20/22, respectively. The mean PPS daily dose was 282 mg (range, 88-400 mg), whereas the mean cumulative dose was 915 g (range, 19-3650 g) over a mean period of 8.8 years (range, 2 months-25 years). There was evidence of retinopathy in 41% of the eyes; DT was identified in 24 eyes (31%) and QT in 8 eyes (10%). Retinal pigment epithelium (RPE) abnormalities (thickening or thinning or both) were present in all eyes with DT. Retinal pigment epithelium atrophy was seen in 7 eyes (9%). In addition to well-established findings, the unique SD-OCT features of this cohort included interdigitation zone abnormalities and the presence of a flying saucer-type defect. Fundus autofluorescence abnormalities were seen in 24 eyes (30.8%), with 20 (66.7%) of these exhibiting abnormalities located outside the central subfield and extending beyond the arcades. Findings from the masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.

Clinical and genetic findings in a Chinese cohort with choroideremia.

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