Iris Pigment Epithelium Research Articles

Anterior segment swept-source optical coherence tomography and ultrasound biomicroscopy in iris and ciliary body lesions

ABSTRACT Objectives Differentiation of iris and ciliary body lesions as benign or malignant and cystic or solid is important. The aim of this study was to compare anterior segment swept-source optical coherence tomography (AS SS-OCT) and ultrasound biomicroscopy (UBM) findings in iris and ciliary body tumors. Research design and methods Forty-two eyes of 38 cases with iris and ciliary body tumors imaged with UBM and AS SS-OCT between September 2018 and September 2023 were evaluated retrospectively. Results Of 42 eyes, 14 had melanoma, 14 iris pigment epithelial (IPE) cysts, 7 nevi, 3 Lisch nodules, 2 iris stromal cysts, 1 pars plana cysts, and 1 iris mammillations. An equivalent (100%) visualization of the anterior tumor margin was obtained with both techniques. Compared to AS SS-OCT, UBM was superior for posterior margin visualization in melanocytic tumors and IPE cysts. Bland-Altman plots demonstrated good agreement between UBM and AS SS-OCT for melanocytic tumors < 2.5 mm in base diameter and < 2 mm in thickness. Conclusions Although, UBM is the gold standard for ciliary body and iridociliary tumors. AS SS-OCT should be considered as an excellent alternative to UBM, especially in minimally elevated iris lesions.

Cysts and Tumors of the Retinal Pigment Epithelium

The iris, ciliary body and retinal pigment epithelium (RPE) can undergo reactive hyperplasia, but true neoplasms of the retinal pigment epithelium are rare. RPE tumors can be benign or malignant. Even malignant variants rarely metastasize locally or distantly. Recognition of RPE tumors is important as they can be clinically confused with uveal melanomas and the prognosis and treatment of these two conditions are completely different. They can be distinguished from melanoma by their clinical, imaging and cytopathological features. While observation is usually sufficient in small and asymptomatic RPE tumors, more aggressive treatments (vitreoretinal surgery, plaque radiotherapy, etc.) may be required depending on the conditions they rarely cause. In this review, it is aimed to convey current literature information under 8 sub-titles by quoting references from relatively new diagnostic tests and researches on the subject.

Secondary glaucoma: Toward interventions based on molecular underpinnings.

Glaucoma is a heterogeneous group of progressive diseases that leads to irreversible blindness. Secondary glaucoma refers to glaucoma caused by a known underlying condition. Pseudoexfoliation and pigment dispersion syndromes are common causes of secondary glaucoma. Their respective deposits may obstruct the trabecular meshwork, leading to aqueous humor outflow resistance, ocular hypertension, and optic neuropathy. There are no disease-specific interventions available for either. Pseudoexfoliation syndrome is characterized by fibrillar deposits (pseudoexfoliative material) on anterior segment structures. Over a decade of multiomics analyses taken together with the current knowledge on pseudoexfoliative glaucoma warrant a re-think of mechanistic possibilities. We propose that the presence of nucleation centers (e.g., vitamin D binding protein), crosslinking enzymes (e.g., transglutaminase 2), aberrant extracellular matrix, flawed endocytosis, and abnormal aqueous-blood barrier contribute to the formation of proteolytically resistant pseudoexfoliative material. Pigment dispersion syndrome is characterized by abnormal iridolenticular contact that disrupts iris pigment epithelium and liberates melanin granules. Iris melanogenesis is aberrant in this condition. Cytotoxic melanogenesis intermediates leak out of melanosomes and cause iris melanocyte and pigment epithelium cell death. Targeting melanogenesis can likely decrease the risk of pigmentary glaucoma. Skin and melanoma research provides insights into potential therapeutics. We propose that specific prostanoid agonists and fenofibrates may reduce melanogenesis by inhibiting cholesterol internalization and de novo synthesis. Additionally, melatonin is a potent melanogenesis suppressor, antioxidant, and hypotensive agent, rendering it a valuable agent for pigmentary glaucoma. In pseudoexfoliative glaucoma, where environmental insults drive pseudoexfoliative material formation, melatonin's antioxidant and hypotensive properties may offer adjunct therapeutic benefits. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.

Ebola Virus Tropism in Ex Vivo Cynomolgus Macaque Ocular Tissues.

Ocular complications of Ebola virus disease are well-documented and long-term sequelae in survivors are common and lead to considerable morbidity. However, little is currently known regarding EBOV's tropism and replication kinetics within the eye. To date, limited studies have utilized in vitro infections of ocular cell lines and analyses of archived pathology samples to investigate these issues. Here, we employed ex vivo cultures of cynomolgus macaque eyes to determine the tropism of EBOV in 7 different ocular tissues: cornea, anterior sclera with bulbar conjunctiva, ciliary body, iris, lens, neural retina, and retina pigment epithelium. We report that, except for neural retina, all tissues supported EBOV replication. Retina pigment epithelium produced the fastest growth and highest viral RNA loads, although the differences were not statistically significant. Immunohistochemical staining confirmed and further characterized infection. This study demonstrates that EBOV has a broad tropism within the eye.

Selective Laser Trabeculoplasty (SLT) for IOP Control in a Patient with Bilateral Acute Iris Transillumination (BAIT)

ABSTRACT Introduction Bilateral acute iris transillumination (BAIT) is a clinical condition characterized by acute bilateral loss of iris pigment epithelium and iris transillumination. Because of the similar presentation, it is commonly confused with anterior uveitis, making it an important differential diagnosis for this condition. Case description We report the case of a 60-year-old male patient who presented all the characteristics of BAIT after undergoing systemic treatment with moxifloxacin and that had the intraocular pressure (IOP) successfully controlled with selective laser trabeculoplasty (SLT). Conclusion SLT might be an effective therapeutic option and should be considered for the control of IOP in BAIT.

Argon laser trabeculoplasty for congenital ectropion uveae: Case report and review of the literature.

A 18-year-old woman with unilateral glaucoma secondary to congenital ectropion uveae (CEU) in the right eye, without other systemic and ocular associations. Intraocular pressure (IOP) was uncontrolled under topical therapy. The visual field (VF) was within normal limits; retinal nerve fiber layer (RNFL) thickness, as evaluated by Optical Coherence Tomography (OCT), was reduced. The patient refused surgical intervention. After evaluation of the iridocorneal angle, ALT was performed as follows: 95 spots were applied for the 270 ° of visible trabecular meshwork using a laser beam diameter of 50 μm, an exposure time of 0.1 s and a power of 750 mw). Mean IOP in the right eye, as evaluated by diurnal tonometric curve, was 10 mmHg, 16 mmHg and 20 mmHg respectively one month, four months and eight months after ALT, with no additional topical therapy, and 18 mmHg twelve months after ALT with topical therapy. CEU is a rare, non-progressive anomaly characterized by the proliferation of iris pigment epithelium on anterior surface of iris; glaucoma, in this disorder, is often poorly controlled with medical therapy alone. In a phase of initial glaucomatous damage and with a not particularly high IOP, as in this case, ALT could be an alternative therapeutic option at least in the short-term, when surgery is not feasible immediately. In fact, given its limited effectiveness over time, ALT can be used as a temporary control measure of IOP, pending surgery to become feasible.

Bilateral Acute Depigmentation of Iris (BADI) and Bilateral Acute Iris Transillumination (BAIT)-An Update.

Bilateral acute depigmentation of the iris (BADI) and bilateral acute iris transillumination (BAIT) are relatively new clinical entities characterized by acute pigment dispersion from the iris stroma or iris pigment epithelium, respectively. While BADI presents with diffuse or geographic areas of iris stromal depigmentation without transillumination, BAIT cases typically develop diffuse iris transillumination and mydriatic atonic pupils. Prolonged pigment dispersion and ocular hypertension are more common in BAIT. Although the exact etiopathogenesis is still unknown, moxifloxacin toxicity appears to be a probable/likely cause. The underlying cause of BADI or BAIT in patients who were not exposed to fluoroquinolone antibiotics remains unexplained. Systemic viral infections, including coronavirus disease 2019, may be the triggering event in several cases.

Bilateral Multiple Primary Cysts of the Iris Pigment Epithelium Occluding Pupil.

Bilateral Multiple Primary Cysts of the Iris Pigment Epithelium Occluding Pupil.

Pigmented floating vitreous cyst

A 6-year-old male reported seeing a floating body in his left eye for a few days. There was no history of ocular trauma or surgery. His visual acuity was 20/20 OD and 20/40 OS, with normal intraocular pressure and a quiet anterior segment. Slit-lamp microscopy revealed a floating, mobile, pigmented mass in the vitreous cavity (Fig. 1A; Supplementary Video 1, available online). Anterior-segment optical coherence tomography revealed a mobile circular cystic mass with hyperechoic thin walls (Fig. 1B). Brain computed tomography and experimental tests for parasitic infection were negative. A diagnosis of iris pigment epithelium cyst was made. The cyst was monitored and remained stable at the 3-month follow-up.

Structure of iris neoplasms in children and adolescents

AIM: To describe clinical cases of iris neoplasms in children and adolescents.&#x0D; MATERIAL AND METHODS: The study was based on retrospective and prospective analyses of children and adolescents with iris neoplasia from January 2018 to April 2022. During this period, 44 children with suspected iris neoplasia, including 20 boys and 24 girls, applied to the outpatient department; their ages ranged from 6 months to 17 years (9.15 years). The diagnosis was based on a comprehensive examination of patients including clinical and instrumental methods. Biomicroscopy, ultrasound investigation including ultrasound biomicroscopy, and when necessary, optical coherence tomography of the anterior eye region were performed. When it was impossible to establish the diagnosis due to the childs age, the examination was performed under general anesthesia in the ocular oncology and radiology department.&#x0D; RESULTS: Of the 44 iris lesions, nevus was found in 32 (72.7%) patients, iris melanosis in 3 (6.8%), cysts in 5 (11.3%), heterochromia in 1 (2.3%), floccula in 1 (2.3%), hamartroma in 1 (2,3%), and melanocytoma in1 (2,3%). The majority of the patients with these lesions are observed in the outpatient department. From January 2018 to April 2022, six children with iris lesions were examined in the department of ophthalmo-oncology and radiology under general anesthesia; accordingly, two children received dynamic observation, two underwent iridectomy, and two others underwent YAG-laser cystotomy and cystodestruction. Two iridectomies were also performed among adolescents. Histological diagnosis was verified in four patients after iridectomy: iris stromal cyst, iris pigment epithelium cyst, melanocytoma, and iris spindle cell nevi were detected.&#x0D; CONCLUSION: According to the observation data, iris nevi were most common (72.7%), followed by cysts (11.3%) and melanosis (6.8%) of the iris. Heterochromia, floccules, and hamartomas, and melanocytoma of the iris had equal frequency (2.3%).

Pigmented Free-Floating Iris Cyst in the Anterior Chamber

A 45-year-old man presented with a free-floating cyst in the anterior chamber of his left eye (Fig A-B). Medical history revealed a blunt trauma by firework to the left eye 10 years prior. Anterior-segment OCT scan revealed a cyst in the anterior chamber with hyperreflective walls and clear hyporeflective lumen (Fig C-D). The optical density is comparable with the anterior chamber fluid. The cyst was examined by a pathologist, which resulted in discovery of an iris cyst derived from iris pigment epithelium (hematoxylin and eosin staining) (Fig E).

Bilateral Acute Iris Transillumination

Bilateral Acute Iris Transillumination is a rare entity characterized by pigment dispersion, raised intraocular pressure and sluggish pupils. It usually follows systemic infections. A mid aged female presented with photophobia, visual blurring and ocular pain. Bilateral ocular examination revealed patchy loss of iris pigment epithelium, pupillary atrophy, and persistent mydriasis and raised intra ocular pressure. She had history of acute respiratory infection treated with oral moxifloxacin one month before onset of her ocular discomfort. Her ocular symptoms were managed with topical pressure lowering drugs and steroids which improved over a period of 6 to 9 weeks, however, pupils remained slightly dilated.

Aperture photometry measurements of melanin particles in Krukenberg spindles of the cornea in pigment dispersion syndrome.

Quantification of melanin pigment release in pigment dispersion syndrome as well as observations of melanin brightness changes can be valuable information in the management of this rare ocular disease. Previous studies have focused on examining the iris pigment epithelium and aqueous humor. Therefore, the aim of this study was to examine the cornea. A novel technique was developed for this purpose based on aperture photometry. Slit lamp digital video images of the cornea were recorded. A single frame from each video recording based on the quality was chosen for further processing and analysis. Aperture photometry was performed with AstroImageJ open source software. Aperture selection was performed automatically. Melanin particles displaying a signal-to-noise ratio above 20 were analyzed. A total of 16 melanin particles from the right eye of the patient participating in the study were detected and a further 9 melanin particles from the left eye. The examined area of the cornea measured 348 × 348 pixels in the image. Brightness differed by as much as 8.98 × among particles in the right eye and 2.03 × in the left eye. It seems feasible for this new method to be potentially used in the monitoring of patients with pigment dispersion syndrome and pigmentary glaucoma as well as in other ocular diseases.

Evaluation of the characteristics of primary iridociliary cysts using ultrasound biomicroscopy at a tertiary care centre

ObjectifPrésenter les caractéristiques des kystes irido-ciliaires primaires à l’échographie biomicroscopique dans un centre de soins tertiaires du Canada. NatureÉtude rétrospective. ParticipantsAu total, 189 patients (212 yeux) ont été adressés au Sinai Health System (Toronto) en raison d'une suspicion d'anomalies de l'iris. MéthodesOn a examiné les dossiers médicaux des patients qui nous ont été adressés entre mars 2016 et octobre 2019. Tous les patients ont été évalués par échographie biomicroscopique et ont reçu un diagnostic de kyste irido-ciliaire. Les données sur l’âge, le sexe, l'atteinte (iris vs corps ciliaire), la latéralité du kyste, sa taille et sa localisation ont été notées lors de l'examen initial et du suivi. RésultatsParmi les 189 patients (212 yeux) qui présentaient un kyste irido-ciliaire, les femmes (65,1 %) étaient plus nombreuses que les hommes (34,9 %). L'incidence la plus élevée a été enregistrée chez les femmes de 21 à 30 ans (13,2 %). L’épithélium pigmentaire de l'iris était touché dans 84,4 % des cas, et seul le corps ciliaire était atteint dans 3,8 % des cas. Le kyste touchait à la fois l’épithélium pigmentaire de l'iris et le corps ciliaire dans 10,8 % des cas. Le diamètre des kystes s’échelonnait de 0,5 à 4,41 mm et dépassait 1 mm dans 78,7 % des cas; 86,8 % des kystes étaient unilatéraux. On comptait 12 % de polykystose, tandis que 8,5 % des kystes étaient multiloculaires; 1 % des kystes présentaient ces deux caractéristiques. Vingt-trois (23) yeux (12,2 %) ont fait l'objet d'une échographie biomicroscopique 1 an plus tard. La taille des kystes irido-ciliaires était demeurée stable, et ces derniers n'avaient pour ainsi dire pas pris de volume dans 73,9 % des cas (n = 17). Cependant, on a observé une augmentation de la taille du kyste irido-ciliaire chez 1 patient après 4 mois. ConclusionOn trouve peu de données sur les kystes irido-ciliaires dans la littérature médicale. L’échographie biomicroscopique est un outil clinique utile pour évaluer les anomalies de l'iris. Les kystes irido-ciliaires ont tendance à demeurer stables au fil du temps et à entraîner peu de complications.

A Rolling Ball in the Eye

A 9-year-old girl presented to our hospital without a medical history. In the left eye, slit-lamp examination revealed that a dark brown spherical object (approximately 1.84 × 1.75 mm) was located at the inferior anterior chamber (Fig A). The 3-dimensional reconstruction showed that a free-floating “ball” could be clearly seen (Fig B). Anterior-segment OCT was performed to evaluate its position in relation to the iris (Fig C). She continues to be observed without further ocular sequela. Primary cysts of the iris pigment epithelium are uncommon, and stationary lesions rarely progress, which require no treatment (Magnified version of Fig A-C is available online at www.aaojournal.org).

Method of surgical treatment of patients with oculocutaneous albinism using artificial iris

To study the results of surgical treatment with implantation of an artificial iris as a diaphragm element in patients with albinism. This article was based on the examination and treatment of 2 patients suffering from oculocutaneous albinism, which is characterized by hypopigmentation of the iris and retinal pigment epithelium of the retina, foveolar hypoplasia, low visual acuity, nystagmus, strabismus and excruciating photophobia. The patients were implanted an artificial iris in both eyes with fixation in the capsular bag in the first patient, and in the ciliary sulcus in the second. In both patients, complaints of photophobia and optical phenomena have ceased. Visual acuity increased to 0.2 and remained without regression throughout the entire period of observation. Intraocular pressure and hydrodynamic parameters also remained stable throughout the observation period. The artificial irises were observed by ultrabiomicroscopy to remain in a stable position both when it was implanted in the capsule bag, and when it was seamlessly fixed in the ciliary sulcus. The surgical interventions relieved patients from glare, at the same time improving visual acuity without correction, as well as achieving a pronounced cosmetic effect and visual rehabilitation. Artificial irises have proven to be a safe and effective way to treat patients with oculocutaneous albinism.

The depigmentation degree of iris pigment epithelium in pseudoexfoliation syndrome

BackgroundTo compare the optical density of iris pigment epithelium (ODIPE) and iris stromal thickness (IST) measurements in patients having pseudoexfoliation syndrome (PXS) and age-gender matched participants. MethodsThis is a cross-sectional study. Patients with PXS were enrolled in the study group. Age and gender-matched healthy subjects with no evidence of PXS were recruited as controls. After a comprehensive ophthalmological evaluation, the anterior segment images were acquired using anterior segment spectral-domain optical coherence tomography (AS SD-OCT). The acquired pictures were further analyzed using the ImageJ program. Two investigators measured the ODIPE and the IST of the subjects, and the repeatability and reproducibility were checked. SPSS program was used for statistical analysis. ResultsThe PXS group was comprised of twenty-two eyes (n = 22 patients), and the control group contained twenty-six eyes of 26 age and gender-matched healthy subjects. The mean temporal ODIPE of the study group was found to be decreased significantly in comparison to the mean temporal ODIPE of the control eye (p = 0.018). Both the mean nasal (N) and temporal (T) ISTs of the PEX eyes were thinner than the control eyes (p = 0.006 and p = 0.002, respectively). The mean baseline IOP was found to significantly negatively correlate with the ODIPE in the PEX group at both N and T sides (r = -0.531, p = 0.011 and r = -0.685, p < 0.001, respectively). ConclusionThe pupillary margin IPE was found more depigmented, and the mean N and T IST were significantly thinner in the PEX group by comparison with the age-gender matched healthy controls. The mean baseline IOP was negatively correlated with the pupillary margin's IPE pigmentation degree in patients with PXS.

Synchrotron-Based Imaging Reveals the Fate of Selenium in Striped Marsh Frog Tadpoles.

Synchrotron-based X-ray fluorescence microscopy (XFM) coupled with X-ray absorption near-edge structure (XANES) imaging was used to study selenium (Se) biodistribution and speciation in Limnodynastes peronii tadpoles. Tadpoles were exposed to dissolved Se (30 μg/L) as selenite (SeIV) or selenate (SeVI) for 7 days followed by 3 days of depuration. High-resolution elemental maps revealed that Se partitioned primarily in the eyes (specifically the eye lens, iris, and retinal pigmented epithelium), digestive and excretory organs of SeIV-exposed tadpoles. Speciation analysis confirmed that the majority of accumulated Se was converted to organo-Se. Multielement analyses provided new information on Se colocalization and its impact on trace element homeostasis. New insights into the fate of Se on a whole organism scale contribute to our understanding of the mechanisms and risks associated with Se pollution.

Zika Virus Infection of Human Iris Pigment Epithelial Cells.

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.

Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy.

Age-related macular degeneration (AMD) is the most frequent cause of blindness in patients >60 years, affecting ~30 million people worldwide. AMD is a multifactorial disease influenced by environmental and genetic factors, which lead to functional impairment of the retina due to retinal pigment epithelial (RPE) cell degeneration followed by photoreceptor degradation. An ideal treatment would include the transplantation of healthy RPE cells secreting neuroprotective factors to prevent RPE cell death and photoreceptor degeneration. Due to the functional and genetic similarities and the possibility of a less invasive biopsy, the transplantation of iris pigment epithelial (IPE) cells was proposed as a substitute for the degenerated RPE. Secretion of neuroprotective factors by a low number of subretinally-transplanted cells can be achieved by Sleeping Beauty (SB100X) transposon-mediated transfection with genes coding for the pigment epithelium-derived factor (PEDF) and/or the granulocyte macrophage-colony stimulating factor (GM-CSF). We established the isolation, culture, and SB100X-mediated transfection of RPE and IPE cells from various species including rodents, pigs, and cattle. Globes are explanted and the cornea and lens are removed to access the iris and the retina. Using a custom-made spatula, IPE cells are removed from the isolated iris. To harvest RPE cells, a trypsin incubation may be required, depending on the species. Then, using RPE-customized spatula, cells are suspended in medium. After seeding, cells are monitored twice per week and, after reaching confluence, transfected by electroporation. Gene integration, expression, protein secretion, and function were confirmed by qPCR, WB, ELISA, immunofluorescence, and functional assays. Depending on the species, 30,000-5 million (RPE) and 10,000-1.5 million (IPE) cells can be isolated per eye. Genetically modified cells show significant PEDF/GM-CSF overexpression with the capacity to reduce oxidative stress and offers a flexible system for ex vivoanalyses and in vivo studies transferable to humans to develop ocular gene therapy approaches.