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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.

Although there is ample evidence that the advanced glycation end-product (AGE) glucosepane contributes to age-related morbidities and diabetic complications, the impact of glucosepane modifications on proteins has not been extensively explored due to the lack of sufficient analytical tools. Here, we report the development of the first polyclonal anti-glucosepane antibodies using a synthetic immunogen that contains the core bicyclic ring structure of glucosepane. We investigate the recognition properties of these antibodies through ELISAs involving an array of synthetic AGE derivatives and determine them to be both high-affinity and selective in binding glucosepane. We then employ these antibodies to image glucosepane in aging mouse retinae via immunohistochemistry. Our studies demonstrate for the first time accumulation of glucosepane within the retinal pigment epithelium, Bruch's membrane, and choroid: all regions of the eye impacted by age-related macular degeneration. Co-localization studies further suggest that glucosepane colocalizes with lipofuscin, which has previously been associated with lysosomal dysfunction and has been implicated in the development of age-related macular degeneration, among other diseases. We believe that the anti-glucosepane antibodies described in this study will prove highly useful for examining the role of glycation in human health and disease.

The term bacillary layer detachment (BLD) represents a possible separation between the myoid and ellipsoid component of the inner segment, following insult or injury to the outer retina. It has been described previously in cases of toxoplasma retinochoroiditis, central serous chorioretinopathy, Vogt Koyanagi Harada disease and trauma.To describe the presence of BLD in Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE).Clinical and OCT-based description of three consecutive cases of APMPPE with BLD.All the three cases (a 25-year-old female, a 36-year-old male, and a 32-year-old male) presented with unilateral, diminution of vision of acute onset. They were diagnosed as APMPPE and OCT revealed a splitting of the ellipsoid zone, resembling a BLD. All the three cases showed complete resolution by 1 week.BLD appears in the acute stage of APMPPE and resolves rapidly within a week.

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.

Placental growth factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family of proteins that participate in angiogenesis and vasculogenesis. Anti-VEGF therapy has become the standard treatment for ocular angiogenic disorders in ophthalmological practice. However, there is emerging evidence that anti-VEGF treatment may increase the risk of atrophy of the retinal pigment epithelium (RPE), which is important for the homeostasis of retinal tissue. Whereas the cytoprotective role of VEGF family molecules, particularly that of VEGF A (VEGFA) through its receptor VEGF receptor-2 (VEGFR-2), has been recognized, the physiological role of PlGF in the retina is still unknown. In this study, we explored the role of PlGF in the RPE using PlGF-knockdown RPE cells generated by retrovirus-based PlGF-shRNA transduction. We show that VEGFA reduced apoptosis induced by serum starvation in RPE cells, whereas the antiapoptotic effect of VEGFA was abrogated by VEGFR-2 knockdown. Furthermore, PlGF knockdown increased serum starvation-induced cell apoptosis and unexpectedly reduced the protein level of VEGFR-2 in the RPE. The antiapoptotic effect of VEGFA was also diminished in PlGF-knockdown RPE cells. In addition, we found that glycogen synthase kinase 3 activity was involved in proteasomal degradation of VEGFR-2 in RPE cells and inactivated by PlGF via AKT phosphorylation. Overall, the present data demonstrate that PlGF is crucial for RPE cell viability and that PlGF supports VEGFA/VEGFR-2 signaling by stabilizing the VEGFR-2 protein levels through glycogen synthase kinase 3 inactivation.

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.]

BackgroundBilateral 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 presentationPatient 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.ConclusionsBilateral 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.

The teleost species Notopterus notopterus (Pallas) possess bundled photoreceptors in their retina. It was found that the margin of the inner portion (the vitreal half) of photoreceptor bundles emits thin processes. Each process terminates on the contralateral photoreceptor bundle, or the processes from adjacent photoreceptor bundle may fuse. The site of the inner half of the photoreceptor bundles from where they arise shows minimal support of the photoreceptor bundles by retinal pigment epithelium, and so it is likely that those accessory structures may aid to hold the photoreceptor bundles in correct orientation.

Purpose: To report a case of bilateral acute iris transillumination (BAIT) in association with coronavirus disease 2019 (COVID-19).Case report: A 44-year-old woman patient presented with decreased visual acuity, pain, photophobia, and redness in both eyes. The patient reported that she had recent close contact with severe acute respiratory syndrome - coronavirus-2 (SARS-CoV-2) case; also, she mentioned that she was hospitalized for bilateral pneumonia for 14 days. On examination, visual acuity of both eyes was 20/40. Slit-lamp biomicroscopy showed bilateral pigment deposition on the corneal endothelium, 4+ pigment dispersion in the anterior chamber, iris depigmentation with iris transillumination defects. Intraocular pressure was measured as 32 mmHg in right eye and 38 mmHg in left eye. The patient was started on bilaterally topical anti-inflammatory and anti-glaucomatous therapy.Conclusion: It is important to keep in mind that ocular manifestations associated with COVID-19 may include rare entities such as BAIT.

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 infectious posterior/panuveitides. 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 appeared to perform sufficiently well for use in clinical and translational research.

To report the changes of trabecular meshwork (TM) pigmentation and clinical outcomes of patients with pigment dispersion syndrome (PDS) after resolution of reverse pupillary block. Twenty one eyes of 11 PDS patients were followed up periodically for 15 years after resolution of reverse pupillary block with either Nd: YAG laser peripheral iridotomy (LPI) or trabeculectomy. Visual acuity (VA), best-corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP), Humphrey visual field analysis (VFA), gonioscopy and stereoscopic funduscopy were performed on admission and every 6 months postoperatively. TM pigmentation was quantitatively evaluated and graded every 5 years after the treatment, in which the circumference of anterior chamber angle was divided into 4 quadrants: superior, inferior, nasal and temporal. Postoperative IOP, VA, BCVA, VFA, TM pigmentation and adjunctive anti-glaucoma medications were main outcome measurements and compared with baseline. Eleven patients (9 males, 2 females) were identified as PDS according to the diagnostic criteria, with average age of 38.25 ± 6.93 years (range, 31–55 years) at initial diagnosis. The mean IOP level was 33.1 ± 9.8 mmHg (range, 22–56 mmHg) at diagnosis. Ten PDS eyes received LPI, and the other eleven eyes underwent uneventful trabeculectomy. The median TM pigmentation score of the 21 PDS eyes was 16 (interquartile range [IQR], 15–16) on admission, which changed to 14 (IQR, 13–15), 13 (IQR, 12–14), 12(IQR, 10.5–12) at 5-, 10-, 15-year follow-up visits respectively. The decrease rate of TM pigmentation was 37% in inferior quadrant, while in nasal, temporal, and superior quadrant the reduction rate was 28%, 23%, and 18%, respectively, at the last follow-up visit. Majority of these enrolled eyes (19/21) had stable VA and BCVA with average endpoint IOP of 15.1 ± 3.4 mmHg. TM pigmentation in PDS patients attenuates with time after reverse pupillary block was resolved, in which the inferior quadrant seems faster than the other quadrants.

Purpose Ciliary epithelium (CE) of adult mammalian eyes contains quiescent retinal progenitor/stem cells that generate neurospheres in vitro and differentiate into retinal neurons. This ability doesn't evolve efficiently probably because of regulatory mechanisms, such as microRNAs (miRNAs) that control pluripotent, progenitor, and differentiation genes. Here we investigate the presence of Let-7 miRNAs and its regulator and target, Lin28 and Hmga2, in CE cells from neurospheres, newborns, and adult tissues. Methods Newborn and adult rats CE cells were dissected into pigmented and nonpigmented epithelium (PE and NPE). Newborn PE cells were cultured with growth factors to form neurospheres and we analyzed Let-7, Lin28a, and Hmga2 expression. During the neurospheres formation, we added chemically modified single-stranded oligonucleotides designed to bind and inhibit or mimic endogenous mature Let-7b and Let-7c. After seven days in culture, we analyzed neurospheres size, number and expression of Let-7, Lin28, and Hmga2. Results Let-7 miRNAs were expressed at low rates in newborn CE cells with significant increase in adult tissues, with higher levels on NPE cells, that does not present the stem cells reprogramming ability. The Lin28a and Hmga2 protein and transcripts were more expressed in newborns than adults cells, opposed to Let-7. Neurospheres presented higher Lin28 and Hmga2 expression than newborn and adult, but similar Let-7 than newborns. Let-7b inhibitor upregulated Hmga2 expression, whereas Let-7c mimics upregulated Lin28 and downregulated Hmga2. Conclusions This study shows the dynamic of Lin28-Let-7-Hmga regulatory axis in CE cells. These components may develop different roles during neurospheres formation and postnatal CE 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.

Copper nanoparticles demonstrate antibacterial activity, but their toxicity to eukaryotic systems is less understood. Here, we carried out a comparative study to determine the biocompatibility and cytotoxicity of sub-10 nm copper nanoparticles to a variety of biological systems, including prokaryotic cells (Escherichia coli), yeast, mammalian cell lines (HEK293T, PC12), and zebrafish embryos. We determined the bearing threshold for the cell-death-inducing concentration of copper nanoparticles by probing cell growth, viability, as well as embryological features. To exclude the partial toxicity effect from the remnant reactants, we developed a purification approach using agarose gel electrophoresis. Purified CuONP solution inhibits bacterial growth and causes eukaryotic cell death at 170 and 122.5 ppm (w/w) during the 18 h of treatment, respectively. CuONP significantly reduces the pigmentation of retina pigmented epithelium of zebrafish embryos at 85 ppm. The cytotoxicity of CuONP in eukaryotic cells could arise from the oxidative stress induced by CuONP. This result suggests that small copper nanoparticles exert cytotoxicity in both prokaryotic and eukaryotic systems, and therefore, caution should be used to avoid direct contact of copper nanoparticles to human tissues considering the potential use of copper nanoparticles in the clinical setting.

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.

Purpose To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA. Design Retrospective analysis of a multicenter, prospective, randomized controlled trial. Participants The Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. Methods We manually delineated GA on 1654 fundus photographs of 365 eyes. We measured GA areas in 9 subfields on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and correlated them with VA via a mixed-effects model. We determined the optimal diameter for the central zone by varying the diameter from 0 to 10 mm until the highest r2 between GA area in the central zone and VA was achieved. We estimated the VA decline rate over 8 years using a linear mixed model. Main Outcome Measures Geographic atrophy area in macular subfields and VA. Results The percentage of area affected by GA declined as a function of retinal eccentricity. GA area was higher in the temporal than the nasal region (1.30 ± 1.75 mm2 vs. 1.10 ± 1.62 mm2; P = 0.005) and in the superior than the inferior region (1.26 ± 1.73 mm2 vs. 1.03 ± 1.53 mm2; P Conclusions The prevalence of GA varies significantly across different macular regions. Although total GA area was associated poorly with VA, GA area in the central 1-mm diameter zone was correlated significantly with VA and may serve as a surrogate endpoint in clinical trials.

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_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.

Usutu virus (USUV), an African mosquito-borne flavivirus closely related to West Nile virus, was first isolated in South Africa in 1959. USUV emerged in Europe two decades ago, causing notably massive mortality in Eurasian blackbirds. USUV is attracting increasing attention due to its potential for emergence and its rapid spread in Europe in recent years. Although mainly asymptomatic or responsible for mild clinical signs, USUV was recently described as being associated with neurological disorders in humans such as encephalitis and meningoencephalitis, highlighting the potential health threat posed by the virus. Despite this, USUV pathogenesis remains largely unexplored. The aim of this study was to evaluate USUV neuropathogenicity using in vivo and in vitro approaches. Our results indicate that USUV efficiently replicates in the murine central nervous system. Replication in the spinal cord and brain is associated with recruitment of inflammatory cells and the release of inflammatory molecules as well as induction of antiviral-responses without major modulation of blood-brain barrier integrity. Endothelial cells integrity is also maintained in a human model of the blood-brain barrier despite USUV replication and release of pro-inflammatory cytokines. Furthermore, USUV-inoculated mice developed major ocular defects associated with inflammation. Moreover, USUV efficiently replicates in human retinal pigment epithelium. Our results will help to better characterize the physiopathology related to USUV infection in order to anticipate the potential threat of USUV emergence., Author summary Number of emerging arboviruses involved in human infections has increased considerably in the past years. Among them, Usutu virus (USUV) is an African mosquito-borne virus first isolated in South Africa that recently emerged. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. Nonetheless, increased cases of neurological complications such as encephalitis or meningoencephalitis have been reported in Europe but the mechanisms behind this neuropathogenesis remain largely unclear. In this study we showed that USUV can infect efficiently several organs and cells of the central nervous system associated with a drastic inflammation and various deleterious effects. Our results contribute to the characterization of the neurotropism related to USUV infection.

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.

Animal pigmentation primarily depends on the presence and mixing ratio of chromatophores, functioning in animal survival and communication. For the benthic and carnivorous Siniperca chuatsi, pigmentation pattern is key to concealment and predation. In this study, the formation, distribution, and main pattern of chromatophores were observed in the embryos, larvae, skins, and visceral tissues from S. chuatsi. Melanophores were firstly visualized in the yolk sac at segmentation stage, and then they were migrated to the whole body and further clustered into the black stripes, bands, and patches. In adult S. chuatsi, the head, black band, and body side skins mainly contained melanophores, showing as deep or light black. The abdomen skin mainly contained iridophores, showing as silvery. In the eye, the pigment layers were located in the epithelial layers of iris and retina and shown as black. Then, the pigmentation-related gene, tyrosinase gene from S. chuatsi (Sc-tyr) was analyzed by bioinformatics and quantitative methods. The Sc-tyr gene encoded a protein with 540 amino acids (Sc-TYR). The Sc-TYR contained two copper ion binding sites, which were coordinated by six conserved histidines (H182, H205, H214, H366, H370, H393) and necessary for catalytic activity. The Sc-TYR was well conserved compared with TYR of various species with higher degree of sequence similarity with other fishes (77.6-98.3%). The qRT-PCR test showed that the Sc-tyr mRNA reached the peak value at segmentation stage in the embryo development, the black skins displayed a higher expression level than that in silvery skin, and the eye had the highest expression level compared with other tissues. Further research on enzyme activity showed that the expression patterns of tyrosinase activity were similar to that of the Sc-tyr mRNA. Comparing with the results of molecular and phenotype, it was found that the temporal and spatial distributions of tyrosinase corresponded well with changes in pigmentation patterns and the intensity of skin melanization. This study initially explored the pigmentation formation and tyrosinase expression, which served as a foundation for further insight into the genetics mechanism of body color formation in S. chuatsi.

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.