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Aims: Adenomas of the ciliary body epithelium, including adenoma of the pigmented ciliary body epithelium (APCE) and adenoma of the non-pigmented ciliary body epithelium (ANPCE), are extremely rare, and most knowledge about them comes from sporadic case reports. The purpose of this study was to provide a comprehensive understanding of adenomas of the ciliary body epithelium and to identify the similarities and differences between APCE and ANPCE., Methods: This study was a retrospective case series comprising data from 41 patients obtained from retrieved publications and five cases diagnosed at the Shanghai Ninth People's Hospital. The clinicopathological features, treatment and prognosis of APCE and ANPCE were compared using the non-parametric rank sum test, t-test and the χ 2 test., Results: The clinical and histopathological features and treatment were analogous between APCE (n=23) and ANPCE (n=23). The overall visual prognosis associated with the two tumours was good, with 63% of the patients having stable or improved vision after treatment. Enucleation was the primary cause of eventual vision loss (three in APCE vs two in ANPCE, p=0.001). Notably, iris invasion was commonly observed in patients with APCE (six in APCE vs zero in ANPCE, p=0.014), and iris invasion was associated with decreased vision eventually (p=0.003). Tumour size was irrelevant to the vision outcome (p=0.65). Metastasis or recurrence did not occur in any of the patients., Conclusion: In most cases, the clinicopathological features of ANPCE and APCE were similar. Iris invasion was commonly observed in patients with APCE, which was associated with poor visual prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report an atypical presentation of an epibulbar simple cartilaginous choristoma with a unique pigmented multicystic component., Case Description: A 69-year-old African American female presented for evaluation of a right nasal epibulbar lesion that had progressed over the prior year. Slit-lamp evaluation revealed an immobile, mildly pigmented multicystic lesion measuring 6.0 × 4.5 mm that involved the nasal bulbar conjunctiva and the plica semilunaris. The lesion appeared benign, without feeder vessels or features of epithelial dysplasia. Given its recent growth and the patient's cosmetic concerns, the lesion was excised with ocular surface reconstruction. Histopathological evaluation disclosed a well-circumscribed nodule of well-differentiated cartilage in the substantia propria, consistent with a simple cartilaginous choristoma. The overlying conjunctival stroma contained multiple cysts lined by focally pigment epithelium. The patient recovered well from surgery, with satisfactory cosmetic results., Conclusions: Our case of epibulbar simple cartilaginous choristoma includes a prominent superficial component of pigmented epithelial cysts, which has not been previously reported in the literature. This augments our knowledge on the spectrum of presentations of cartilaginous choristomas and underscores the importance of histopathological evaluation for definitive diagnosis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To describe an atypical presentation of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in a patient with ankylosing spondylitis (AS) receiving secukinumab., Methods: Retrospective chart review., Results: A 48-year-old female patient with AS receiving secukinumab complained of impaired vision in her left eye. Left eye examination revealed multiple yellow-white lesions at the posterior pole and central subfoveal fluid.The lesions regressed without scarring. The case was diagnosed with clinically APMPPE., Conclusion: In AS patients, posterior uveitis can manifest as APMPPE. It should be recorded as an entity to be considered in the differential diagnosis.

Bruch's membrane resides in the subretinal tissue and regulates the flow of nutrients and waste between the retinal pigment epithelial (RPE) and vascular layers of the eye. With age, Bruch's membrane becomes thicker, stiffer, and less permeable, which impedes its function as a boundary layer in the subretina. These changes contribute to pathologies such as age-related macular degeneration (AMD). To better understand how aging in Bruch's membrane affects surrounding tissues and to determine the relationship between aging and disease, an in vitro model of Bruch's membrane is needed. An accurate model of Bruch's membrane must be a proteinaceous, semipermeable, and nonporous biomaterial with similar mechanical properties to in vivo conditions. Additionally, this model must support RPE cell growth. While models of subretinal tissue exist, they typically differ from in vivo Bruch's membrane in one or more of these properties. This study evaluates the capability of membranes created from recombinant hagfish intermediate filament (rHIF) proteins to accurately replicate Bruch's membrane in an in vitro model of the subretinal tissue. The physical characteristics of these rHIF membranes were evaluated using mechanical testing, permeability assays, brightfield microscopy, and scanning electron microscopy. The capacity of the membranes to support RPE cell culture was determined using brightfield and fluorescent microscopy, as well as immunocytochemical staining. This study demonstrates that rHIF protein membranes are an appropriate biomaterial to accurately mimic both healthy and aged Bruch's membrane for in vitro modeling of the subretinal tissue.

The outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the extracellular matrix compartment named Bruch's membrane, situated between the retinal epithelium and the choroid. Like many tissues, the retina experiences age-related structural and metabolic changes, which are relevant for understanding major blinding diseases of the elderly, such as age-related macular degeneration. Compared with other tissues, the retina mainly comprises postmitotic cells, making it less able to maintain its mechanical homeostasis over the years functionally. Aspects of retinal ageing, like the structural and morphometric changes of the pigment epithelium and the heterogenous remodelling of the Bruch's membrane, imply changes in tissue mechanics and may affect functional integrity. In recent years, findings in the field of mechanobiology and bioengineering highlighted the importance of mechanical changes in tissues for understanding physiological and pathological processes. Here, we review the current knowledge of age-related changes in the outer retina from a mechanobiological perspective, aiming to generate food for thought for future mechanobiology studies in the outer retina., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The article presents two clinical cases of adenocarcinoma of nonpigmented epithelium of the ciliary body, which is a very rare malignant tumor of the organ of vision with distinctive features. Surgical treatment is necessary to verify this tumor and assess the degree of its aggressiveness in terms of the prognosis of the disease, with subsequent pathomorphological and immunohistochemical studies. The article also discusses the epidemiological aspects, morphological features, clinical manifestations of this pathological condition, as well as possible treatment options and features of follow-up monitoring of this group of patients.

Epithelial cysts run a high risk of recurrence and conversion to sheet-like ingrowth after surgical intervention. In this retrospective study, we introduced a modified iridectomy for treatment of secondary epithelial iris cysts (EICs) in the anterior chamber. Twenty-nine patients (29 eyes) aged 2-61 years received "open iridectomy" for EICs between April 1995 and July 2019. After viscodissection, most of the cyst wall was cut using a 20-gauge aspiration cutter via a 2.5-mm clear corneal incision. The residue closely adhering to the iris stroma was remained to avoid photophobia and diplopia. At 3 months, best corrected visual acuity was ≥ 20/100 in 55.5% (15/27, except two pediatric patients with poor cooperation) of patients. Among the eight patients suffering partial corneal edema preoperatively, six patients received surgery treatment at 3-6.5 months, and the cornea in the other two patients became transparent after medication. In a mean follow-up of 47.4 months, recurrence occurred in 3 patients at 7, 37, and 118 months, respectively. The percentage of treatment success was 96%, 87%, and 65% at 1, 5, and 10 years, respectively. "Open iridectomy" was effective for EICs, with a minimal invasion, less damage to the corneal endothelium, and a low recurrence rate., (© 2021. The Author(s).)

Purpose: To determine classification criteria for acute posterior multifocal placoid pigment epitheliopathy (APMPPE)., Design: Machine learning of cases with APMPPE and 8 other posterior uveitides., Methods: Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the posterior uveitides. The resulting criteria were evaluated on the validation set., Results: One thousand sixty-eight cases of posterior uveitides, including 82 cases of APMPPE, were evaluated by machine learning. Key criteria for APMPPE included (1) choroidal lesions with a plaque-like or placoid appearance and (2) characteristic imaging on fluorescein angiography (lesions "block early and stain late diffusely"). Overall accuracy for posterior uveitides was 92.7% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for APMPPE were 5% in the training set and 0% in the validation set., Conclusions: The criteria for APMPPE had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To find immunohistochemical markers that distinguish adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) from metastatic carcinoma, especially metastatic renal cell carcinoma., Design: Retrospective case series., Methods: Three cases of adenocarcinoma of the NPCE were examined histologically with hematoxylin-eosin stain and immunohistochemical stains including vimentin, AE1/AE3, Cam 5.2, CK7, PAX2, PAX8, AMACR, and CAIX. We also reviewed previously reported cases of this tumor., Results: We found that the immunohistochemical profile of adenocarcinoma of the NPCE can overlap with renal cell carcinoma. Both tumors can express vimentin, cytokeratin AE1/AE3, Cam 5.2, PAX2, PAX8, and AMACR. One of the adenocarcinomas of the NPCE in our series also expressed CD10 and the renal cell carcinoma marker (RCC Ma). Carbonic anhydrase IX (CAIX) was not detected in any of the 3 tumors., Conclusions: Adenocarcinomas arising in phthisic eyes can be diagnostically challenging. We have found it particularly difficult to distinguish adenocarcinoma of the NPCE from metastatic carcinoma, especially metastatic clear cell renal cell carcinoma and papillary renal cell carcinoma. Because of the immunophenotypic overlap, most patients will require systemic workup including imaging of the kidneys to be certain of the diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

During recent Zika epidemics, adults infected with Zika virus (ZIKV) have developed organ-specific inflammatory complications. The most serious Zika-associated inflammatory eye disease is uveitis, which is commonly anterior in type, affecting both eyes and responding to corticosteroid eye drops. Mechanisms of Zika-associated anterior uveitis are unknown, but ZIKV has been identified in the aqueous humor of affected individuals. The iris pigment epithelium is a target cell population in viral anterior uveitis, and it acts to maintain immune privilege within the anterior eye. Interactions between ZIKV and human iris pigment epithelial cells were investigated with infectivity assays and RNA-sequencing. Primary cell isolates were prepared from eyes of 20 cadaveric donors, and infected for 24 hours with PRVABC59 strain ZIKV or incubated uninfected as control. Cytoimmunofluorescence, RT-qPCR on total cellular RNA, and focus-forming assays of culture supernatant showed cell isolates were permissive to infection, and supported replication and release of infectious ZIKV. To explore molecular responses of cell isolates to ZIKV infection at the whole transcriptome level, RNA was sequenced on the Illumina NextSeq 500 platform, and results were aligned to the human GRCh38 genome. Multidimensional scaling showed clear separation between transcriptomes of infected and uninfected cell isolates. Differential expression analysis indicated a vigorous molecular response of the cell to ZIKV: 7,935 genes were differentially expressed between ZIKV-infected and uninfected cells (FDR < 0.05), and 99% of 613 genes that changed at least two-fold were up-regulated. Reactome and KEGG pathway and Gene Ontology enrichment analyses indicated strong activation of viral recognition and defense, in addition to biosynthesis processes. A CHAT network included 6275 molecular nodes and 24 contextual hubs in the cell response to ZIKV infection. Receptor-interacting serine/threonine kinase 1 (RIPK1) was the most significantly connected contextual hub. Correlation of gene expression with read counts assigned to the ZIKV genome identified a negative correlation between interferon signaling and viral load across isolates. This work represents the first investigation of mechanisms of Zika-associated anterior uveitis using an in vitro human cell model. The results suggest the iris pigment epithelium mounts a molecular response that limits intraocular pathology in most individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ryan, Carr, Furtado, Ma, Ashander, Simões, Oliver, Granado, Dawson, Michael, Appukuttan, Lynn and Smith.)

Purpose: To evaluate choroidal area, stroma/lumen ratio, choriocapillaris vessel density, and choriocapillaris flow area in eyes with central serous chorioretinopathy, uncomplicated pachychoroid, and pachychoroid pigment epitheliopathy using enhanced depth imaging-optical coherence tomography and optical coherence tomography angiography., Materials and Methods: This retrospective study analyzed enhanced depth imaging-optical coherence tomography and optical coherence tomography angiography scans of 142 eyes of 92 patients with central serous chorioretinopathy, uncomplicated pachychoroid, and pachychoroid pigment epitheliopathy. The choroidal area and stroma/lumen ratio were measured by binarization of enhanced depth imaging-optical coherence tomography images. Choriocapillaris vessel density and choriocapillaris flow area were measured at the choriocapillaris level by manual segmentation of optical coherence tomography angiography scans., Results: The mean stroma/lumen ratio results were 0.361, 0.345, and 0.354 in central serous chorioretinopathy, uncomplicated pachychoroid, and pachychoroid pigment epitheliopathy groups, respectively ( p  > 0.05). The mean whole image choriocapillaris vessel density in uncomplicated pachychoroid group was higher compared with central serous chorioretinopathy and pachychoroid pigment epitheliopathy groups ( p  < 0.0001). The mean foveal, parafoveal, and perifoveal choriocapillaris vessel densities were lower in central serous chorioretinopathy group than in uncomplicated pachychoroid group ( p  < 0.0001). The mean choriocapillaris flow area was lower in central serous chorioretinopathy group than in uncomplicated pachychoroid and pachychoroid pigment epitheliopathy groups ( p  < 0.0001 and p  = 0.01, respectively)., Conclusion: Our findings suggest that both choroidal vessels and stroma are equally involved in central serous chorioretinopathy, uncomplicated pachychoroid, and pachychoroid pigment epitheliopathy. The choriocapillaris segment seems to be more affected in central serous chorioretinopathy compared to uncomplicated pachychoroid and pachychoroid pigment epitheliopathy. However, the reduced optical coherence tomography angiography signal in central serous chorioretinopathy group could be due to shadowing artifact or choriocapillaris hypoperfusion and further studies with higher quality imaging tools are needed.

The terms "congenital grouped albinotic spots" (CGAS) and "polar bear tracks" refer to a rare, benign retinal disorder of unknown etiology characterized by multiple, predominantly unilateral, variably sized, well-circumscribed, flat white retinal spots organized in groups. To date, very few cases of CGAS have been reported. The authors describe a case of CGAS thoroughly characterized by multimodal imaging over an 8-year follow-up, aiming to provide new insights on the pathophysiology of this entity. This is the first report where a long follow-up combined with up-to-date imaging technology is used to characterize CGAS. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:236-238.]., (Copyright 2020, SLACK Incorporated.)

Objectives: To report the clinical and demographic characteristics, imaging findings, treatment results, and follow-up data of patients with iris cysts., Materials and Methods: The medical records of 37 patients with iris cysts were retrospectively analyzed. Ultrasound biomicroscopy (UBM), swept-source optical coherence tomography (SS-OCT), and SS-OCT angiography (SS-OCTA) were performed to examine the iris cysts., Results: The mean age of the patients was 34.4 years, ranging from 5 to 85 years. Twenty-four patients (65%) were female and 13 (35%) were male. Mean follow-up period was 21.3 months, ranging from 4 months to 8 years. Thirty-five (94.5%) of the cysts were classified as primary and 2 (4.5%) were classified as secondary. Thirty-one (83.7%) of the primary cysts were pigment epithelial and 4 were stromal. Primary iris pigment epithelial (IPE) cysts were classified as peripheral in 26 patients (72.2%), midzonal in 4 (11.1%), and dislodged in 1 (2.7%). Stromal cysts were classified as acquired in 3 patients (8.1%) and congenital in 1 patient (2.7%). Secondary iris cysts were caused by perforating eye injury. UBM could visualize both the anterior and posterior surfaces of the cysts (26 patients). Anterior segment SS-OCT could visualize the anterior but not the posterior surface of the cysts (4 patients). Iris cysts did not display intrinsic vascularity on SS-OCTA (4 patients). All pigment epithelial cysts were managed by observation. Of the 4 primary stromal cysts, 3 were managed by surgical excision and 1 by observation. Two secondary cysts required surgical removal., Conclusion: Pigment epithelial cysts generally remain stable without need for treatment. However, iris stromal cysts frequently require surgical intervention. UBM and SS-OCT were valuable in the diagnosis of iris cysts. On UBM, iris cysts appear with a thin, hyperechoic wall with hypoechoic internal content. Iris cysts did not have intrinsic vascularity on anterior segment SS-OCTA.

Placoid pigment epitheliopathy and serpiginous choroiditis are among the white dot retinal syndromes and possess similarities that can cause confusion between these two diseases. However, they are very different in terms of their progression and prognosis, which requires a diagnosis of certainty in order to better manage the patients with the diseases and identify potentially serious progressive complications. The clinical presentation, results of testing, differential diagnoses and treatment of these two pathologies are discussed in this article., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background : To evaluate the long-term progression of autosomal recessive retinitis pigmentosa (RP) due to mutations in KIZ using multimodal imaging and a quantitative analytical approach. Methods : Whole exome sequencing (WES) and targeted capture sequencing were used to identify mutation. Fundus photography, short-wavelength autofluorescence (SW-AF), spectral-domain optical coherence tomography (SD-OCT) imaging, and electroretinography (ERG) were analyzed. Serial measurements of peripheral retinal pigment epithelium (RPE) atrophy area with SW-AF, as well as the ellipsoid zone (EZ) width using SD-OCT were performed. Results : Two homozygous variants in KIZ-a c.226C>T mutation as well as a previously unreported c.119&#95;122delAACT mutation-were identified in four unrelated patients. Fundus examination and ERG revealed classic rod-cone dysfunction, and SD-OCT demonstrated outer retinal atrophy with centrally preserved EZ line. SW-AF imaging revealed hyperautofluorescent rings with surrounding parafoveal, mid-peripheral and widespread loss of autofluorescence. The RPE atrophy area increased annually by 4.9%. Mean annual exponential rates of decline for KIZ patients were 8.5% for visual acuity and 15.9% for 30 Hz Flicker amplitude. The average annual reduction distance of the EZ distance was 66.5 μm per year. Conclusions : RPE atrophy progresses along with a loss of photoreceptors, and parafoveal RPE hypoautofluorescence is commonly seen in KIZ- associated RP patients. KIZ -associated RP is an early-onset severe rod-cone dystrophy.

Background: Bilateral Acute Depigmentation of the Iris (BADI) is a condition which was first described in a case series from Turkey by Tugal-Tutkin and Urgancioglu in (Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006). The condition is characterized by bilateral acute depigmentation and discoloration of the iris stroma, pigment dispersion, and deposition of pigment in the angle. In our case we report a patient who developed BADI after receiving pitcher plant extract injections for chronic migraine, while her identical twin sister has normal iris architecture and pigmentation and never received any pitcher plant injections., Case Presentation: Patient is a 41-year-old female with history of pitcher plant extract injections to her face for chronic migraine, who later developed bilateral depigmentation of the iris. She did not have any signs of anterior segment uveitis or iridocyclitis. She has an identical twin sister who maintained normal iris pigmentation during the entire course., Conclusions: Bilateral Acute depigmentation of the is a recently discovered condition described in the literature in Turkish patients (Tugal-Tutkun and Urgancioglu, Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006; Tugal-Tutkun et al., Ophthalmology 116(8):1552-7, 2009). This condition affects mainly young females and is characterized by acute bilateral stromal depigmentation, without other pathologic ocular findings. These patients usually maintain normal vision and do not develop significant glaucoma from pigment collecting in the anterior chamber angle. This condition can be mistaken for Fuchs' heterochromic iridocyclitis, pigment dispersion syndrome, pseudoexfoliation syndrome, and viral iridocyclitis. This is the first reported case in North America and is important for differentiation from the above pathologies. Our patient had a history of pitcher plant extract injections to the face but it is unclear if this is associated with our patient's development of BADI. As awareness of this condition progresses, a possible etiology may be elucidated.

In classic familial adenomatous polyposis (FAP) adenomas become malignant. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a retinal pigmented lesion and is the earliest and most common potential extraintestinal manifestation of FAP. This review aims to summarize and analyse all of the published data on CHRPE in patients with classic FAP and then ascertain whether these patients should undergo a relatively cheap and non-invasive dilated fundus examination to screen for CHRPE. Adhering to Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines our database search identified 102 relevant articles of which 13 were selected for further analysis. The percentage of FAP patients with CHRPE was found to be 80.00%, whereas the percentage of at-risk patients with CHRPE was 31.12%. Despite various statistically significant findings, CHRPE alone cannot be used as a surrogate for diagnosing FAP in those with a positive family history. The authors advocate a combined approach of eye examinations, colonoscopy and genetic testing., (© 2019 Royal Australian and New Zealand College of Ophthalmologists.)

Competing Interests: None

Purpose: Pathogenic variants of the G-protein coupled receptor 143 (GPR143) gene may result in Ocular albinism type I (OA1). In this study, we describe the clinical features and investigate the GPR143 gene mutations in six Chinese families with OA1 and evaluate the thickness changes of iris for the affected males and female carriers., Methods: Families were ascertained, and patients underwent complete ophthalmologic examinations, including the best corrected visual acuity (BCVA), anterior segment of the eyes, vitreous and fundus changes. Spectral domain optical coherence tomography (SD-OCT) was used to measure the full iris thickness, the stroma/anterior border (SAB) layer, and the posterior epithelial layer (PEL) at the pupillary and ciliary regions. DNA was extracted from the peripheral blood vessels after confirmed consent information. GPR143 gene was directly sequenced by the Sanger method., Results: The affected males had variable reduced visual acuity, nystagmus and macular hypoplasia. Four novel frameshift mutations and two previously reported missense/nonsense mutations in the GPR143 gene were detected in these families. The thickness of the iris was significantly reduced at the ciliary region in the affected males, compared with that in the normal controls and the female carriers., Conclusions: Pathogenic variants in the GPR143 gene may disturb the normal melanogenesis in the pigmented tissues of the eye, result in macular hypoplasia, and alter the thickness of the iris., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose : To describe the phenotype and genotype in a young woman with Danon disease. Methods : The patient underwent an ophthalmic examination including best corrected visual acuity (BCVA), fundus photography and fundus autofluorescence (FAF), full-field electroretinography (full-field ERG), multifocal ERG, optical coherence tomography (OCT) and SAP-Humphrey 30-2 at the ages of 20 and 25. Electrooculography, fluorescein angiography (FA), indocyanine angiography and OCT angiography were performed only once. Genetic testing using a Next-Generation Sequencing panel and immunohistochemical analysis of LAMP2 protein expression were performed in the patient's explanted heart, and the patient's cardiologic and ophthalmologic records were retrospectively reviewed. Results : A de novo , novel, mosaic mutation, c.135dupA; p.(Trp46Metfs*10) was identified in exon 2 of the LAMP2 gene. Immunohistochemical investigation of the myocardium in the explanted heart revealed pronounced deficiency of LAMP2 protein in cardiomyocytes. The color photographs, FAF images and FA revealed more extensive peripheral pigmentary retinal dystrophy (PPRD) at the 5-year follow-up examination. No changes were observed in BCVA, OCT, SAP-Humphrey 30-2 or multifocal ERG findings at follow-up. Full-field ERG showed an asymmetric interocular reduction in ERG response at follow-up: the b-wave amplitude of the rod response had decreased by 29% in the right eye, but by only 6 % in the left eye. The a-wave amplitude of single-flash response had decreased by 9 % in the left eye, while it had increased by 3% in the right eye. Conclusions : Although PPRD progressed slowly, it was an important clue in the diagnosis of the life-threatening condition of Danon disease.

To analyze features of the choriocapillaris in eyes with earlier stages of pachychoroid spectrum, this study included 46 eyes with PPE, 32 age-matched eyes with pachychoroid without epitheliopathy, and 30 normal controls. Macular 3 × 3 mm 2 angiographic images were obtained with swept-source optical coherence tomography. Vascular density and signal void area in the choriocapillaris were analyzed. Topographical correlation of signal voids with the dilated choroidal large vessel (pachyvessel) was assessed. Choriocapillaris vascular density was significantly lower in eyes with PPE compared with controls (p = 0.003). The number, the total area and the average size of signal voids was the highest in the PPE group followed by the pachychoroid without epitheliopathy and then controls (all p ≤ 0.001). 89.0% signal void area colocalized with pachyvessels. The average size of the signal void was higher if it was colocalized with pachyvessel (p < 0.001). In conclusion, the area of flow impairment in the choriocapillaris was increased in eyes with pachychoroid and even greater when epitheliopathy was present. Pachyvessel was associated with choriocapillaris flow impairment by location and size.

Purpose: To compare the difference in the rate of survival of unaffected fellow eyes between choroidal neovascularization (CNV) in the first eyes and retinal angiomatous proliferation (RAP) in the first eyes., Design: Cohort retrospective study., Participants: A total of 329 consecutive patients enrolled in our Eye Clinic between February 2006 and November 2014 were involved in the study. Only patients with naïve unilateral forms of neovascularization in 1 eye were included in this study., Methods: A clinical database containing patients' data and ocular history was evaluated. Only patients with naive lesions in 1 eye and without signs of neovascular AMD in the fellow eye were included in the analysis. The time of absence of neovascularization in the fellow eye was calculated., Main Outcome Measures: Survival of the fellow eye was estimated by Kaplan-Meier analysis, and log-rank test was used to compare CNV and RAP fellow eye survival., Results: A total of 202 eyes affected by CNV and 39 eyes affected by RAP were enrolled in the study. The mean follow-up time was 2.9 years (range, 182-2461 days) for CNV and 2.6 years (range, 519-1504 days) for RAP. Kaplan-Meier analysis showed that the 50% of the fellow eyes with CNV did not develop neovascularization for 5.3 years, whereas the 50% of the fellow eyes with RAP did not develop neovascularization for 3.5 years. Log-rank test showed a highly significant difference between the 2 curves (P < 0.002)., Conclusions: This study showed that the incidence of neovascularization in the unaffected fellow eye increases with time, and when the first eye is affected by RAP, the development of a lesion in the second eye is more premature., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Significance: Patients with pigment dispersion syndrome are frequently encountered in clinical practice. Iris abnormalities and the absence of key features of pigment dispersion syndrome can guide the discovery of secondary causes of pigmentary glaucoma, such as peripheral iris pigment epithelial cysts., Purpose: The purpose of this study was to describe a patient initially diagnosed as having primary pigmentary glaucoma found to have multiple bilateral peripheral iris pigment epithelial cysts causing pigment liberation, focal angle closure, and advanced secondary glaucoma., Case Report: A 64-year-old man presented for follow-up after a recent diagnosis of primary pigmentary glaucoma in the left eye. Clinical examination revealed transillumination defects of both irides and a heavily pigmented trabecular meshwork. A midperipheral bulge of the iris was appreciated in the superior temporal quadrant of the left eye. Gonioscopic evaluation showed that the bulge focally obstructed the angle. Anterior segment optical coherence tomography demonstrated a normal iris insertion of both eyes, with the exception of a steepened approach superotemporally in the left eye. Ultrasound biomicroscopy revealed bilateral small- to medium-sized peripheral iris pigment epithelial cysts and confirmed a large cyst superotemporally in the left iris., Conclusions: This case describes a patient with advanced secondary pigmentary glaucoma from iris pigment epithelial cysts. The mechanisms of glaucoma are likely twofold: (1) pigment liberation from the cysts contacting the lens zonules and, to a lesser extent, (2) focal angle closure at the site of the large peripheral cyst. The key features of pigmentary glaucoma, namely, posterior bowing of the iris, may not be present in secondary pigment dispersion. This case highlights the importance of careful evaluation of the iris and angle in making a correct diagnosis. The choice of topical agent to control intraocular pressure while not increasing the size of these cysts is also an important consideration.

Objective : To describe the clinical and Anterior Segment Swept-Source Optical Coherence Tomography (AS-SS OCT) findings in Bilateral Acute Depigmentation of the Iris (BADI). Design : Retrospective descriptive study of three clinical cases. Results : Three women diagnosed with BADI shared a history of bacterial infections treated with moxifloxacin. The AS-SS OCT showed damage from the collarette to the root of the iris, without affecting the pupillary area. In the affected areas, the anterior edge had lost its homogeneous hyper-reflectivity. The stroma was thinned and showed a patchy and diffused hyper-reflectivity. The pigmentary epithelium appeared unaffected. Conclusions : AS-SS OCT findings, not previously described, locate the damage in BADI in the anterior edge and iridian stroma, areas which are rich in melanocytes and permeable to aqueous humor.

Purpose: To determine rate of bone spicule pigmentation appearance in patients with retinitis pigmentosa (RP)., Design: Retrospective, observational case series., Participants: A total of 240 patients were analyzed for this study., Methods: A retrospective analysis was conducted at the Electrodiagnostic Clinic at Columbia University Medical Center of all patients' medical records with a diagnosis of RP between July 2017 and January 2018. The medical records of these patients were analyzed to determine whether the patients presented with pigment migration on their first and last visit to our clinic. Among those who did not have bone spicule at first visit, we examined the time to appearance of newly formed bone spicule. The survival distribution was then estimated using the Kaplan-Meier estimator, where the event is bone spicule and time starts at first visit., Results: From the 240 patients analyzed, 213 patients presented with intraretinal pigmentation on the first visit to our clinic, and 27 patients presented without intraretinal pigmentation. Of these 27 patients, 10 patients developed pigmentation by their follow-up, with a median time to appearance of bone spicule of 5.4 years from first visit, according to the Kaplan-Meier estimates., Conclusions: The timeline of bone spicule pigment appearance in RP has important implications in the natural history characterization of disease progression and application as a biomarker for interventional trials., (Published by Elsevier Inc.)

Purpose: In this study, we elucidated the effects of berberine, a major alkaloid component contained in medicinal herbs, such as Phellodendri Cortex and Coptidis Rhizoma, on expression of monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in a human retinal pigment epithelial cell line (ARPE-19) caused by lipopolysaccharide (LPS) stimulation., Methods: ARPE-19 cells were cultured to confluence. Berberine and LPS were added to the medium. MCP-1 and IL-8 mRNA were measured by real-time polymerase chain reaction. MCP-1 and IL-8 protein concentrations in the media were measured using enzyme-linked immunosorbent assay., Results: After stimulation with LPS, MCP-1 and IL-8 mRNA in ARPE-19 cells reached maximum levels at 3 h, and MCP-1 and IL-8 protein in the culture media reached maximum levels at 24 h. Berberine dose-dependently inhibited MCP-1 and IL-8 mRNA expression of the cells and protein levels in the media stimulated with LPS., Conclusions: These findings indicate that berberine inhibited the expression of MCP-1 and IL-8 induced by LPS.

Competing Interests: There are no conflicts of interest

Purpose: It is widely accepted that RPE melanin has a protective effect against oxidative damage in RPE cells. It is possible that an additional protective characteristic of melanin is the ability to modulate RPE cell immune response. In this study, in vitro modeling was used to probe the relationship between RPE pigmentation and immune response by monitoring IL-6 expression and secretion in calf melanin pigmented ARPE-19 cells seeded onto glycated extracellular matrix as a stressor., Methods: ARPE-19 cells were left unpigmented or were pigmented with either calf melanin or latex beads, and were then seeded onto RPE-derived extracellular matrix (ECM) or tissue culture-treated plates (no ECM). ECMs were modified by glycation. IL-6 expression was measured using qPCR and IL-6 secretion was determined using an ELISA, both at 30 min and 24 h after seeding. MTT assay was used to quantify cell attachment to glycated matrices 30 min after seeding. In unpigmented ARPE-19 cells, rate of cell attachment to substrate was monitored for 60 min after seeding using a hemacytometer to count unattached cells. Additionally, cell viability was evaluated using the Neutral Red assay 24 h after seeding., Results: A significant increase in IL-6 expression was observed in calf melanin pigmented cells versus latex bead and unpigmented controls (p < 0.0001) 30 min after seeding onto ECM. Twenty-four hours after seeding, a significant decrease in IL-6 expression was observed in calf melanin pigmented cells (p < 0.0001) versus controls, implicating down-regulation of the cytokine. Additionally, calf melanin pigmented cell populations showed significant increase in attachment compared to unpigmented controls on either no ECM or unmodified ECM., Conclusions: Pigmentation of RPE cells with calf melanin resulted in significant changes in IL-6 expression regardless of ECM modification, in vitro. These findings suggest that melanin in the RPE may participate in immune response modulation in the retina with particular regard to cell attachment to protein substrates. The results of this study further implicate the role of chemical changes to melanin in regulating inflammation in retinal disease.

Iris cysts, both primary and secondary, are a diagnostic and treatment challenge. Primary cysts arise either from the iris pigment epithelium or the iris stroma. Posterior pigment epithelial cysts are subdivided according to their location as central, midzonal, and peripheral. Iris stromal cysts are classified either as congenital or acquired. Free-floating cysts are usually dislodged pigment epithelial cysts. Secondary cysts are classified according to the underlying cause as implantation cysts, drug-induced, uveitic, tumor-induced, parasitic, or as cysts associated with systemic disorders. Differential diagnosis is based on the clinical presentation and imaging. Ultrasound biomicroscopy is the gold standard for the imaging of iris cysts, combining excellent resolution with sufficient tissue penetration. Treatment of iris cysts depends largely on whether they become symptomatic or not. Symptoms include obstruction of the visual axis, corneal decompensation, secondary uveitis, and secondary glaucoma. Treatment options cover a range from simple observation to fine-needle aspiration (with or without intracystic injection of absolute alcohol or antimitotic agents), laser (argon, Nd:YAG), or surgical excision. In the past, the prevailing notion was that of a radical surgical intervention in the form of iridectomy or iridocyclectomy. Given the high rate of recurrence, a stepwise conservative approach is currently favored by most clinicians., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To describe severe bilateral iris depigmentation and persistent ocular hypotony as end-stage manifestations of untreated Vogt-Koyanagi-Harada disease., Methods: We present the clinical findings and diagnostic studies performed for three patients with bilateral iris depigmentation., Results: Vogt-Koyanagi-Harada disease in late recurrent stage was diagnosed in three patients with bilateral severe iris depigmentation and persistent ocular hypotony., Conclusions: Early diagnosis and treatment of inflammation are crucial factors in the clinical outcome of Vogt-Koyanagi-Harada disease. When left undiagnosed and untreated from early stages, severe iris depigmentation and ocular hypotony, uncommon manifestations of this disease, can develop.

Importance: Solar retinopathy is a rare form of retinal injury that occurs after direct sungazing., Objective: To enhance understanding of the structural changes that occur in solar retinopathy by obtaining high-resolution in vivo en face images., Design, Setting, and Participant: Case report of a young adult woman who presented to the New York Eye and Ear Infirmary with symptoms of acute solar retinopathy after viewing the solar eclipse on August 21, 2017., Main Outcomes and Measures: Results of comprehensive ophthalmic examination and images obtained by fundus photography, microperimetry, spectral-domain optical coherence tomography (OCT), adaptive optics scanning light ophthalmoscopy, OCT angiography, and en face OCT., Results: The patient was examined after viewing the solar eclipse. Visual acuity was 20/20 OD and 20/25 OS. The patient was left-eye dominant. Spectral-domain OCT images were consistent with mild and severe acute solar retinopathy in the right and left eye, respectively. Microperimetry was normal in the right eye but showed paracentral decreased retinal sensitivity in the left eye with a central absolute scotoma. Adaptive optics images of the right eye showed a small region of nonwaveguiding photoreceptors, while images of the left eye showed a large area of abnormal and nonwaveguiding photoreceptors. Optical coherence tomography angiography images were normal in both eyes. En face OCT images of the right eye showed a small circular hyperreflective area, with central hyporeflectivity in the outer retina of the right eye. The left eye showed a hyperreflective lesion that intensified in area from inner to middle retina and became mostly hyporeflective in the outer retina. The shape of the lesion on adaptive optics and en face OCT images of the left eye corresponded to the shape of the scotoma drawn by the patient on Amsler grid., Conclusions and Relevance: Acute solar retinopathy can present with foveal cone photoreceptor mosaic disturbances on adaptive optics scanning light ophthalmoscopy imaging. Corresponding reflectivity changes can be seen on en face OCT, especially in the middle and outer retina. Young adults may be especially vulnerable and need to be better informed of the risks of viewing the sun with inadequate protective eyewear.

Purpose: To investigate choroidal involvement in acute posterior multifocal placoid pigment epitheliopathy (APMPPE)., Methods: A retrospective observational case series using multimodal imaging including optical coherence tomography (OCT) angiography., Results: Five patients with APMPPE were included. In most acute lesions, OCT angiography revealed outer retinal and retinal pigment epithelium (RPE) hyperreflective lesions with attenuated OCT signal in the underlying choroid, but careful examination allowed us to identify a single lesion with decreased choriocapillaris flow outside the signal attenuation. Optical coherence tomography angiography obtained after healing of lesions revealed areas of hypointense circular flow voids clustered in groups surrounded by either isointense or hyperintense signal background. Point-by-point evaluation revealed these flow voids did not correspond to areas of RPE thickening or focal pigmentary changes. Larger hypointense lesions were observed and did correlate with pigmentary changes., Conclusion: Our case series demonstrates choriocapillaris flow abnormalities in acute APMPPE extending beyond the OCT lesions, and distinct residual vascular abnormalities in healed APMPPE lesions on OCT angiography. Our findings support a primary ischemic insult to the photoreceptors and RPE, but choriocapillaris flow abnormalities could be secondary to (OCT invisible) retinal and RPE involvement. The lack of understanding of the etiology along with the inability to visualize most of the choroid in acute lesions precludes definite conclusions about the true pathogenesis of APMPPE.

Background: Vitreous cysts are rare clinical findings and seldom cause visual disturbance. They are generally classified as congenital or acquired and are considered idiopathic when the etiology can not be determined. A previous electron microscopic observation on an idiopathic pigmented vitreous cyst has confirmed its pigment epithelial origin. However, the specific kind of pigment epithelium involved remains unclear., Case Presentation: A 39-year-old female presented with a round-shaped floater causing frequent visual disturbance in the left eye. A pigmented, non lobulated and freely mobile vitreous cyst was observed in the anterior vitreous by slit lamp examination and anterior segment optical coherence tomography. The pigment clumps on the cyst wall showed no autofluorescence. No persistent hyaloid artery or connection between the cyst and ocular structures was found by fundus fluorescein angiography and B-scan ultrasound. Serum tests for cysticercoids, sparganosis and toxoplasma were negative. A diagnosis of idiopathic vitreous cyst was made and no intervention was given. The cyst sank to the inferior part of the vitreous and the patient felt less visual disturbance during one-year follow-up., Conclusions: We described the features of a pigmented vitreous cyst revealed by autofluorescence and anterior segment optical coherence tomography for the first time. The intact retina, the absence of lipofuscin of the cyst and its location in the anterior vitreous led to the hypothesis that the cyst may originate from the ciliary pigment epithelium rather than the retinal pigment epithelium.

Purpose: Adenocarcinomas or adenomas derived from pigmented ciliary epithelium (APCE) are exceptionally rare ocular tumors. These tumors have pigmented and epithelioid features, and some APCEs are negative for keratin markers and positive for melanocytic markers. It is especially difficult to distinguish APCEs from uveal melanoma (UM). Accordingly, we examined protein expression and genetic mutations associated with APCE to facilitate diagnosis., Methods: Five APCE and 11 UM samples were obtained from patients during surgical resection at our institute. APCE and UM ocular structures were compared comprehensively. Protein expression and genetic alterations involved in malignant melanoma were evaluated., Results: SOX10 was expressed diffusely in all 11 UMs and in surrounding uveal or choroidal melanocytes, but not in the APCEs or nontumorous pigmented epithelia. Additionally, the expression patterns of cytokeratins and melanocytic markers differed between UMs and APCEs. We identified BRAF V600E mutations in four of five APCE samples, but not in the 11 UM samples. Moreover, GNAQ or GNA11 mutations were found in 10 of the 11 UM samples, but not in APCE samples. NRAS mutations were not observed in either tumor group examined., Conclusions: APCE is a separate entity distinguished from UM by the absence of SOX10 expression and presence of the BRAF V600E mutation. These results have implications for diagnosis, providing a means to distinguish between UM and APCE.

Background: The culture of retinal progenitors from an accessible adult stem cell source such as the limbus could provide a useful autologous source of retinal cell therapies. The human corneoscleral limbus contains multipotent stem cells that can be cultured as floating neurospheres. Previous work in rodents has demonstrated neuronal and photoreceptor differentiation from limbal neurosphere cultures. Here, this study has examined undifferentiated cultured adult human limbal neurospheres as donor cells for retinal cell therapies by transplantation into a rat model of retinal degeneration., Methods: Gene expression in limbal neurospheres was examined by immunostaining and western blot. Human limbal neurospheres were transplanted into the subretinal space of Royal College of Surgeon's rats. Rats were monitored by optical coherence tomography for 6 weeks then processed for retinal histology., Results: Human limbal neurospheres expressed the neural lineage markers, Nestin, sex determining region box-2 and N-cadherin, and the retinal transcription factors microphthalmia-associated transcription factor, sex determining region box-2 and orthodentical homeobox-2. Human limbal neurospheres could be cultured to express NeuN, neurofilament and rhodopsin. Rats receiving saline or no injection underwent complete degeneration of the retinal outer nuclear layer after 3 weeks. In contrast, rats injected with human limbal neurospheres or retinal pigment epithelial cells maintained the outer nuclear layer for up to 6 weeks. Gene expression in transplanted limbal neurospheres was inconsistent with the production of mature retinal pigment epithelial or photoreceptor cells., Conclusions: Human limbal neurospheres represent an accessible source of autologous donor cells for the treatment of retinal diseases., (© 2017 Royal Australian and New Zealand College of Ophthalmologists.)

Few cases have been reported describing choroidal vasculature in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using optical coherence tomography (OCT) angiography. We report choroidal vasculature changes in an APMPPE patient with the clinical course characterized by OCT angiography. A 39-year-old female was referred to us for bilateral multiple white spots in bilateral fundus. The best-corrected visual acuity was 20/20 in the right eye and 20/50 in the left eye. Multiple yellowish-white placoid lesions were observed in bilateral fundus, and fluorescein angiography showed a "block early, stain late" pattern at the placoid lesions characteristic of APMPPE. The placoid lesion represented vascular rarefaction at the choriocapillaris in the OCT angiography en face view. While the clinical course of symptoms and most of the low vascular rarefaction lesions regressed in 6 months, some new lesions were subclinically noted. Blurred vision recurred at 9 months from the first visit, and the vascular rarefaction lesions developed in different areas than those observed in the initial visit. Multiple yellowish-white placoid lesions in an APMPPE patient represented vascular rarefaction at the choriocapillaris in OCT angiography. The vascular rarefaction recovered and then recurred during the clinical course. OCT angiography can visualize changes of the choroidal vessels during APMPPE.

This report describes a case of unilateral pigmented paravenous retinochoroidal atrophy (PPRCA) in a patient with low-grade unilateral intermediate uveitis. A 31-year-old woman, previously diagnosed with intermediate uveitis in the right eye (OD) presented to the clinic. Best-corrected visual acuity was 20/20 OD. Fundus examination, fluorescein angiography, autofluorescence, and optical coherence tomography OD were in keeping with a phenotypic diagnosis of PPRCA. Electrophysiology showed severe photoreceptor dysfunction of both the rod and the cone systems OD. Systemic workup revealed QuantiFERON-gold positive. This is the first report of unilateral PPRCA secondary to presumed ocular tuberculosis. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:345-349.]., (Copyright 2017, SLACK Incorporated.)

A 21-month-old boy presumptively diagnosed with combined hamartoma of the retina and retinal pigment epithelium was found to have juvenile X-linked retinoschisis with vitreomacular traction and prominent retinal folding., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Several tumors and pseudotumors can arise from the iris pigment epithelium (IPE), ciliary pigment epithelium (CPE), and retinal pigment epithelium (RPE), including cysts of the IPE, solitary congenital hypertrophy of the RPE (CHRPE), multifocal CHRPE ("bear tracks"), congenital simple hamartoma of the RPE, combined hamartoma of the retina and RPE, and acquired epithelioma of IPE, CPE, and RPE. This article describes examples of pigment epithelial tumors and pseudotumors by reviewing the literature and cases on file in the Oncology Service at Wills Eye Hospital. Solitary CHRPE, traditionally believed to be stationary, can show growth in diameter in 83% and can spawn elevated nodular tumors that can progressively enlarge, cause complications, and even evolve into malignant epithelioma (adenocarcinoma). Multifocal CHRPE (congenital grouped pigmentation) has no relationship to familial adenomatous polyposis or Gardner syndrome, despite its similarity to the pigmented fundus lesions seen with those conditions. Congenital simple hamartoma of the RPE is a specific lesion that involves the fovea and does not tend to cause complications. Combined hamartoma, an idiopathic proliferation of RPE cells, blood vessels, and glial cells, is also believed to be a relatively stable lesion but can cause vision loss due to traction. Acquired tumors (adenoma, adenocarcinoma) have features distinct from melanoma clinically and histopathologically. Torpedo maculopathy is a small stable lesion with typical features, resembling a torpedo. There are several intriguing tumors and pseudotumors of the pigmented epithelium that have major clinical and histopathologic importance., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)

Purpose: EFEMP1 (fibulin-3) is mutated in Malattia Leventinese/Doyne's honeycomb retinal dystrophy (ML/DHRD), an inherited macular dystrophy similar to AMD. Both ML/DHRD and AMD are characterized by the presence of sub-RPE deposits. Efemp1 knockout mice do not develop sub-RPE deposits. This study was to test whether sub-RPE deposits can be induced in Efemp1 knockout mice by experimentally applied stress conditions that cause wild-type mice to develop sub-RPE deposits., Methods: Efemp1 knockout and control mice at 6, 18, or 24 months old were fed with a synthetic high-fat diet (HFD). Beginning 1 month after starting the HFD, one group of mice was exposed to cigarette smoke daily for 1 month, and another group of mice was subjected to photochemical injury every other day for 2 weeks from a 488-nm argon laser. After the treatments, histologic analysis was performed to assess whether sub-RPE deposits were induced., Results: Basal laminar deposits (BLamDs), a form of sub-RPE deposits, were observed in the 18- and 24-month-old wild-type mice but not in Efemp1 knockout mice in any age groups after exposure to HFD and cigarette smoke or laser injury., Conclusions: Mice lacking fibulin-3 do not develop sub-RPE deposits. Environmental oxidative stressors (HFD/cigarette smoke or HFD/laser) known to cause BLamD formation in wild-type mice failed to induce BLamD formation in Efemp1 knockout mice. These results suggest that fibulin-3 is a central player in the development of BLamD, and deletion of fibulin-3 is protective against the development of BLamD.