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The cilium was one of the first organelles observed through a microscope. Motile cilia appear as oscillating cell appendages and have long been recognized to function in cell motility. In contrast, the far more widespread non-motile cilia, termed primary cilia, were thought to be vestigial and largely ignored following their initial description over a century ago. Only in the last two decades has the critical function of primary cilia been elucidated. Primary cilia play essential roles in signal transduction, chemical sensation, mechanosensation and light detection. Various microscopy approaches have been important for characterizing the structure, dynamics and function of the cilia. In this review, we discuss the application of live-cell imaging technologies and their contribution to our current understanding of ciliary processes.

Objective Patients have shown a lowering of intraocular pressure (IOP) after cataract surgery. Histopathology studies have reported trabecular meshwork (TM) changes in pseudophakic eyes with posterior chamber intraocular lens (PCIOL) and have eluded to the mechanisms for IOP decrease. Unlike PCIOLs, TM histopathology changes after implantation of an anterior chamber intraocular lens (ACIOL) have not been studied, to our knowledge. Therefore, this study aims to examine the histopathological changes in both the TM and corneal endothelium among donor eyes with ACIOL, PCIOL, and phakic eyes. Methods Forty fixed postmortem donor eyes were obtained, sectioned, and embedded. Slides were stained with Masson's trichrome and CD31 vascular endothelial antibody, and further digitalized. Customized Medical Parachute TMAN software quantified the cellular components, the trabecular extracellular matrix (ECM), ECM fibrosis, and trabecular area. Schlemm's canal and corneal endothelium were quantified across the ACIOL, PCIOL, and phakic groups. Results Cellular area component of the TM was lower in the ACIOLs and PCIOLs than in phakic eyes, but statistically significant only between PCIOL and phakic eyes (p = 0.0023). ECM area component, TM fibrosis score and TM lamellae area, ciliary process fibrosis, and CD31 expression in Schlemm's canal showed no differences (p = 0.40, 0.99, 0.10, 0.83, 0.45). Significantly lower corneal endothelial cells were seen in ACIOLs compared with both PCIOLs and phakic eyes (p = 0.0002). Conclusions ACIOLs and PCIOLs in our sample group showed that there is loss of cellular components in the TM compared with the phakic eyes, with PCIOLs displaying the least amount of TM cells statistically, in this cohort. The ACIOLs led to a greater loss of corneal endothelial cells than both PCIOLs and phakic eyes after cataract surgery. The endothelial cells in Schlemm's canal did not seem to be affected by the IOL placements. Therefore, this study illustrates that there are histopathological differences seen with the placements of ACIOLs in both TM and cornea.

Objective The purpose of this study was to compare the acute histological effects of MicroPulse transscleral cyclophotocoagulation (MPCPC) using the MicroPulse P3 Device and continuous wave transscleral cyclophotocoagulation (CWCPC) on the ciliary body and adjacent structures in human cadaver eyes. Methods Quadrants of 6 human cadaver eyes from 3 different donors were subjected to traditional CWCPC, slow burn CWCPC, MPCPC, or no treatment (internal control). Sutures were used to differentiate different treatment areas on each eye. Differential inking was applied after treatments to aid in microscopic correlation. All specimens were subject to standard histologic processing. Tissue sections were cut at 4 microns and stained with hematoxylin and eosin according to established protocols. Pathologic evaluation by light microscopy was confirmed by a senior pathologist blinded to treatment groups. Results In all 6 eyes, tissues treated with traditional and low burn CWCPC showed variable coagulative tissue damage to the ciliary body compared with untreated tissues. Minimal histologic changes were identified within the ciliary processes, although variable pigment clumping and streaming were noted within the pigmented ciliary epithelium. In contrast to CWCPC, MPCPC-treated tissues showed only minimal coagulative tissue damage to the ciliary body. Variable pigment clumping and streaming, however, were also noted in the pigmented ciliary epithelium in MPCPC-treated tissues. Conclusions In human cadaver eyes, MPCPC treatment caused less tissue disruption to the ciliary body compared with traditional and low burn CWCPC treatments. MPCPC may be a less destructive and more selective method of cyclophotocoagulation when compared with traditional and low burn CWCPC.

STUDY QUESTIONDoes age affect endometrial gene expression?SUMMARY ANSWERUsing unsupervised artificial intelligence methods, we report for the first time that endometrial gene expression changes from 35 years of age in women.WHAT IS KNOWN ALREADYFemale fertility declines with age, largely attributed to declining oocyte quality and ovarian reserve. Combined with other evidence, a longstanding paradigm holds that age does not affect the endometrial function and age has not been controlled for properly in endometrial studies.STUDY DESIGN, SIZE, DURATIONA retrospective in silico analysis was performed of endometrial transcriptomic data from the Gene Expression Omnibus (GEO) sample repository for 27 women of different ages. Results were validated in an independent gene expression dataset of 20 endometrial samples from women aged 23–43 years.PARTICIPANTS/MATERIALS, SETTING, METHODSA systematic search was performed in GEO from October 2016 to January 2019 to identify transcriptomic studies involving women of different ages. Included samples were from norm-ovulatory, women of reproductive age (23–49 years) with regular menstrual cycles who were free of endometriosis and used as controls in a previous endometrial study. We used raw gene expression data and metadata from these samples to investigate the effect of age on endometrial gene expression. Files were downloaded, pre-processed and explored for potential confounding variables and outliers. Artificial intelligence methods were applied to define age groups, and differential expression and functional analyses were applied to demonstrate and understand the effect of age on gene expression at the molecular level. Functional results were validated in an independent gene expression dataset of 20 endometrial samples from women aged 23–43 years.MAIN RESULTS AND THE ROLE OF CHANCEAnalysis of the initially retrieved endometrial datasets revealed the age of participants was not available (33.33%) or traceable (43.33%) in most studies. However, one study was suitable for age analysis (GSE4888, n = 27, 23–49 years). Samples showed different transcriptomic profiles according to age, beginning at 35 years. A total of 5778 differentially expressed genes and 27 significantly altered endometrial functions (false discovery rate (FDR) < 0.05) were associated with endometrial gene expression changes related to age. Interestingly, 81.48% of affected functions were related to up-regulation of ciliary processes, with 91 genes involved in cilia motility and ciliogenesis. Other functions included dysregulation of the vascular endothelial growth factor signalling pathway and inhibition of epithelial proliferation triggered by 37 genes involved in cell cycle arrest, angiogenesis, insulin signalling and telomere protection. These findings were validated in an independent dataset using a non-targeted approach; 20 up-regulated ciliary processes (FDR < 0.02) and 6 down-regulated functions related to cell cycle arrest were identified as affected by age, among other hallmarks of ageing such as DNA repair inhibition or sugar metabolism (FDR < 0.05).LARGE SCALE DATAData underlying this article are available in GEO, IDs: GSE4888 (main dataset) and GSE102131 (validation dataset).LIMITATIONS, REASONS FOR CAUTIONThis study is limited in size, as are most studies of endometrial transcriptomics where whole-transcriptome analysis considers nearly 22 000 variables in a relatively small population. Yet, our study includes a main sample set and subsequent validation set that enhances reproducibility of our results and provides reasonable evidence for concluding that age affects endometrial gene expression. A larger study prospectively controlling for patient characteristics is needed to accurately describe changes related to age, with a higher sample size and across a wide age range. Additional studies also are necessary to determine the endometrial ageing contribution to infertility for ultimate translation to a clinical setting.WIDER IMPLICATIONS OF THE FINDINGSOur findings support an influence of age on the endometrium in a genome-wide functional approach, breaking the endometrial ageing paradigm in human reproduction. To our knowledge, this work is the first to identify, using a genome-wide functional non-targeted approach, ciliary processes as the primary dysregulated function associated with maternal age. These results should guide the research community to control for age as a potential confounding variable in endometrial gene expression studies and to consider endometrial ageing in further studies as a potential cause of infertility in the clinical setting. The reported functional dysregulations could contribute to diminished embryo implantation with age and further studies will demonstrate if such dysregulation underlies some cases of implantation failure. Additionally, the discovery of these functional alterations could enable mechanistic studies, particularly around the age-related increase in uterine pathologies.STUDY FUNDING/COMPETING INTEREST(S)This research was funded by the Instituto de Salud Carlos III through Miguel Servet programme (CP20/00118) granted to Patricia Diaz-Gimeno (Spanish Government) co-funded by FEDER; and by IVI Foundation (1706-FIVI-041-PD). A.D.-P. (FPU/15/01398) and A.P.-L. (FPU18/01777) are granted by the pre-doctoral programme fellowship from the Ministry of Science, Innovation and Universities (Spanish Government). The authors do not have any competing interests to declare.TRIAL REGISTRATION NUMBERN/A

The main purpose of glaucoma treatment is to reduce the intraocular pressure (IOP) to a target level. One of the pathogenetically justified method of treatment for various types of glaucoma, first of all its refractory forms, is the surgery on the ciliary body. A purpose of such manipulations is to suppress excessive formation of aqueous humor. Previously, diode laser cyclophotocoagulation was widely used, which is mainly applied in terminal glaucoma. Technological innovations have led to the development of perspective, more safe, and less destructive methods of cyclodestructive anti-glaucomatous operations, such as micro-pulse diode cyclophotocoagulation, endoscopic cyclophotocoagulation, and ultrasound cyclodestruction. During micro-pulse cyclophotocoagulation, the effect of laser energy occurs by short pulses at rest intervals, which significantly reduces the absorption of energy by surrounding tissues and their associated damage. With endoscopic cyclophotocoagulation, the epithelium of the ciliary processes is directly coagulated, which makes it possible to dose laser energy under visual control. Ultrasonic cyclodestruction causes a coagulation necrosis of the ciliary processes with a very insignificant collateral damage of surrounding tissues. Today these surgical techniques are becoming more relevant in the treatment of refractory glaucoma in order to preserve visual functions. This review is an analysis of modern literature, reflecting the efficacy and safety of cyclodestructive operations with sufficiently high visual functions.

Purpose To compare the histologic effects of endoscopic cyclophotocoagulation (ECP) with other ciliary body ablative procedures. A secondary aim was to correlate these findings with historical clinical success and complication rates. Design Prospective, qualitative comparison of histopathologic tissue analysis. Participants Two eyes of two patients who had undergone ECP for open-angle glaucoma were studied. Two eyes from a healthy monkey were treated with ECP and studied. For comparison, 1 eye each of patients who had undergone contact and noncontact neodymium:yttrium–aluminum–garnet transscleral cyclophotocoagulation (TCP) for open-angle glaucoma were analyzed. Methods The human globes were enucleated and submitted for analysis by gross examination and light and electron microscopy. Monkey eyes were studied by gross examination and light microscopy 1 week, 2 weeks, and 1 month after ECP. Main Outcome Measures Gross and histopathologic specimens of all eyes were analyzed with respect to location and type of tissue effects and degree of collateral damage. Results The gross analysis of all ECP specimens showed a uniform anterior-to-posterior whitening of each treated ciliary process. This correlated with microscopic evidence of loss of pigmentation from the pigmented ciliary epithelial cells seen with mostly preserved architecture and vasculature of the ciliary processes. By comparison, the TCP specimens showed erratic treatment of the ciliary processes with overlap into the pars plicata of the ciliary body. Microscopic analysis revealed significant disruption of the cells throughout the ciliary processes and loss of vessels within the stroma. Conclusions Treatment with ECP results in less overall tissue destruction and a targeted effect on the pigmented ciliary epithelium of the ciliary processes when compared with TCP.

Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and we lack tools to identify and treat PMLs at risk for progression to cancer. Here we report the identification of four molecular subtypes of PMLs with distinct differences in epithelial and immune processes based on RNA-Seq profiling of endobronchial biopsies from high-risk smokers. The Proliferative subtype is enriched with bronchial dysplasia and exhibits up-regulation of metabolic and cell cycle pathways. A Proliferative subtype-associated gene signature identifies subjects with Proliferative PMLs from normal-appearing uninvolved large airway brushings with high specificity. In progressive/persistent Proliferative lesions expression of interferon signaling and antigen processing/presentation pathways decrease and immunofluorescence indicates a depletion of innate and adaptive immune cells compared with regressive lesions. Molecular biomarkers measured in PMLs or the uninvolved airway can enhance histopathological grading and suggest immunoprevention strategies for intercepting the progression of PMLs to lung cancer., Bronchial premalignant lesions can potentially progress to lung squamous cell carcinoma. Here, the authors profile bronchial biopsies from high-risk smokers by RNA sequencing and identify four molecular subtypes of premalignant lesions and an immune molecular signature that associates with lesion progression.

The light-sensitive outer segment organelle of the vertebrate photoreceptor cell is a modified cilium filled with hundreds of flattened 'disc' membranes that provide vast light-absorbing surfaces. The outer segment is constantly renewed with new discs added at its base every day. This continuous process is essential for photoreceptor viability. In this review, we describe recent breakthroughs in the understanding of disc morphogenesis, with a focus on the molecular mechanisms responsible for initiating disc formation from the ciliary membrane. We highlight the discoveries that this mechanism evolved from an innate ciliary process of releasing small extracellular vesicles, or ectosomes, and that both disc formation and ectosome release rely on the actin cytoskeleton.

Background This is a case of spontaneous toric implantable collamer lens (TICL) rotation that occurred twice in the left eye of a patient. Case presentation A 24-year-old gentleman received TICL implantation for treatment of myopic astigmatism encountered with spontaneous rotation of approximately 90° from its original position. TICL reposition procedure was performed with visual outcome of 20/16. Surprisingly, a re-rotation of TICL occurred. The patient underwent a replacement of non-toric ICL with a larger size after careful re-evaluation with final visual outcome of 20/20. A short and small ciliary process with shallow ciliary sulcus and posteriorly positioned ciliary body was found by Ultrasound Biomicroscopy (UBM). Conclusions The unique morphology of the ciliary body may have a potential association with the vault and instability of implanted ICL. Careful examination of the ciliary body morphology is essential in preoperative evaluation.

We developed a methodology for 3D assessment of ciliary body of the eye, an important, but understudied tissue, using our new 3D ultrasound biomicroscopy (3D-UBM) imaging system. The ciliary body produces aqueous humor, which if not drained properly, can lead to increased intraocular pressure and glaucoma, a leading cause of blindness. Most medications and some surgical procedures for glaucoma target the ciliary body. Ciliary body is also responsible for focusing-accommodation by muscle contraction and relaxation. UBM is the only imaging modality which can be used to visualize structures behind the opaque iris, such as ciliary body. Our 3D-UBM acquires several hundred high resolutions (50 MHz) 2D-UBM images and creates a 3D volume, enabling heretofore unavailable en face visualizations and quantifications. In this study, we calculated unique 3D biometrics from automated segmentation using deep learning (UNet). Our results show accuracy of 0.93 ± 0.01, sensitivity of 0.79 ± 0.07 and dice score of 0.72 ± 0.07 on deep learning segmentation of ciliary muscle. For an eye, volume of ciliary body was 67.87 mm3, single ciliary process volumes were 0.234 ± 0.093 mm3 with surface areas adjacent to aqueous humor of 3.02 ± 1.07 mm2. Automated and manual measurements of ciliary muscle volume and cross-sectional area are compared which show overestimation in volume measurement but higher agreeability in cross-sectional area measurements.

Background The use of opioids among people of the young and working age has sharply increased in recent years simultaneously with the outbreak observed in the general population. Objective To determine the trigger mechanism of the destructive effect of narcotic analgesics on the ultrastructural level of the vascular tunic of the eyeball. Methods: This experimental study was performed on 26 male rats aged 3.0 months and body weight 160–180 g with daily intramuscular injection of Nalbuphine hydrochloride during 4 weeks. The material for the study was represented by ultramicroscopic sections of the vascular tunic of the eyeball. Results In comparison with the control group there was observed swelling of the cytoplasm and the nuclei of endotheliocytes, considerably narrowed lumens of the capillaries. Plasmolemma of endotheliocytes forms protrusions into the lumen of endotheliocytes forming microvilli. Changes of destructive nature took place in the elements of the smooth endoplasmic reticulum and mitochondrial complex. Signs that are characteristic of sclerosis were found in the surrounding connective tissue complex. In particular, lesions of endothelium and basement membrane of the elements of hemomicrocirculatory bloodstream, epithelium of the ciliary processes, cellular and non-cellular elements of the iris and the uvea proper have studied. Conclusion The databased on the experimental model allow extrapolation the results obtained to humans. It is confirmed that the development of angiopathy is the trigger mechanism of the destructive effect of narcotic analgesics.

Background The visual system of desert rodents demonstrates a rather high degree of development and specific features associated with adaptation to arid environment. The aim of this study is to carry out a descriptive investigation into the most relevant features of the sand rat eye. Results Light microscopic observations revealed that the eye of Psammomys obesus diurnal species, appears similar to that of others rodent with characteristic mammalian organization. The eye was formed by the three distinct layers typical in vertebrates: fibrous tunic (sclera and cornea); vascular tunic (Iris, Ciliary body, Choroid); nervous tunic (retina). Three chambers of fluid fundamentals in maintaining the eyeball’s normal size and shape: Anterior chamber (between cornea and iris), Posterior chamber (between iris, zonule fibers and lens) and the Vitreous chamber (between the lens and the retina) The first two chambers are filled with aqueous humor whereas the vitreous chamber is filled with a more viscous fluid, the vitreous humor. These fluids are made up of 99.9% water. However, the main features, related to life style and arid environment, are the egg-shaped lens, the heavy pigmentation of the middle layer and an extensive folding of ciliary processes, thus developing a large surface area, for ultrafiltration and active fluid transport, this being the actual site of aqueous production. The ciliary muscle is poorly developed and the dilator pupillae is not apparent. Conclusions The ocular globe of sand rat demonstrates a high degree of development and several specific features associated with adaptation to life style and arid environment.

The objective was to assess the effect of high intensity focused ultrasound (HIFU) on intraocular pressure (IOP) in dogs with primary glaucoma (PG). Seven dogs (13 eyes) presenting with PG as diagnosed by a raised IOP (> 20 mm Hg) associated with consistent gonioscopy and ultrasound biomicroscopy of the ciliary cleft, with no other ocular disease. Patients were divided into 3 groups, corresponding to their pre-operative IOP (group 1 ranging from 21 to 30 mm Hg, group 2 from 31 to 40 and group 3 for 40 and above). Ciliary process sonication was achieved with a probe containing one high-frequency transducer operating at 21 MHz during 5 seconds. Six sites were treated in patients from group 1, 8 in group 2, 10 in group 3, under general anesthesia. Post-operative treatment consisted of systemic meloxicam and topical carbonic anhydrase inhibitors, beta-blockers and prostaglandins analogues. No intraoperative complications were observed. Conjunctival hyperaemia occurred in eyes from group 2 (66%) and 3 (100%). Conjunctival burns were visible in 2 patients from group 3. One patient from group 3 experienced a hypertensive spike during the first hours post-op with associated pain. The hypotensive effect of HIFU was observed in all groups. Normotensive IOP (≤20 mm Hg) was reached in all patients until the last recheck at 6 months post op. Despite the small number of patients included in the study, HIFU appears to be a promising option for the management of PG in dogs.Keywords: Ciliary cleft, Dog, Primary glaucoma, Sonication, Surgery

Purpose To measure the anterior and posterior ocular biometric characteristics concurrently and to explore the relationship between iris, ciliary body and choroid in acute primary angle closure eyes (APAC) and fellow eyes. Methods It is a prospective, cross-sectional study. Thirty patients with recent APAC were finally enroled in it. Anterior and posterior uveal parameters were measured simultaneously by anterior segment optical coherence tomography (AS-OCT), swept-source optical coherence tomography (SS-OCT) and ultrasound biomicroscopy (UBM). The parameters were measured including: pupil diameter (PD); iris thickness, curvature (ICURV), area (IAREA); anterior chamber depth (ACD), width (ACW), area (ACA), volume (ACV); lens vault (LV); choroidal thickness and retinal thickness; maximum ciliary body thickness (CBTmax); ciliary body thickness at the point of the scleral spur (CBT0) and 1000 mm away (CBT1000); anterior placement of the ciliary body (APCB); and trabecular-ciliary angle (TCA). Results Compared with fellow eyes, APAC eyes had narrower anterior biometric parameters and presented with smaller anterior segment parameters (including ACD and ACW); (p

Purpose To compare the histopathological morphometry of the trabecular meshwork and ciliary processes in pseudophakic eyes and phakic eyes using advanced image analyzer technology. Setting McGill University, Montreal, Quebec, Canada. Design Retrospective case series. Methods Thirty-five pseudophakic eyes and 25 phakic eyes were sectioned and converted into digital slides. The total trabecular meshwork area and the ciliary body stroma were demarcated. The area of the trabecular meshwork, cellular and noncellular trabecular meshwork compartments, trabecular space, distance from scleral spur to inner uveal trabecular portion, and degree of fibrosis of the ciliary processes were evaluated. Results The trabecular meshwork area was larger in the pseudophakic group than the phakic group (P = .03). Furthermore, a trend of larger trabecular space recorded was seen in the pseudophakic group than the phakic group (P = .14). No differences in the proportion of cellular (P = .88) and noncellular trabecular meshwork compartments (P = .4) were seen between groups. The scleral spur to inner uveal trabecular portion distance was longer in the pseudophakic group than the phakic group (P = .008) and correlate with the trabecular meshwork area (P = .0001, r = 0.56). In the ciliary processes, a higher degree of fibrosis was measured in the pseudophakic group than the phakic group (P = .02). Conclusions There were significant histopathological changes in the trabecular meshwork and higher fibrosis in the ciliary processes in pseudophakic eyes compared with phakic eyes. These findings support the hypothesis that trabecular meshwork remodeling after cataract surgery is involved in lowering intraocular pressure.

We report the clinical features, treatments, and outcomes of 9 infants with glaucoma secondary to congenital fibrovascular pupillary membrane. The clinical features included unilateral low vision, high intraocular pressure (IOP), enlarged and cloudy cornea, loss of anterior chamber, and pupillary membrane. All patients underwent membranectomy, peripheral iridectomy, pupilloplasty, and goniosynechialysis as primary treatment. The membranes were posterior to the iris in all 9 eyes. In 5 eyes, the membrane covered the ciliary processes, and in 1 eye the membrane reached the posterior lens capsule. Following primary surgery, 3 patients developed membrane recurrence, 4 had refractory elevated IOP, and 2 developed lens opacities. All 4 eyes with poor postoperative IOP control had iris root insertion anterior to the scleral spur. Five patients received additional surgeries including membranectomy, pupilloplasty, goniosynechialysis, cyclocryotherapy, ciliary photocoagulation, Amhed valve implantation, and lensectomy. One patient had refractory elevated IOP at last follow-up. IOP in the other 8 eyes was well controlled. None of the affected eyes was able to fix and follow at last follow-up.

SIGNIFICANCE The study provides a new theory on the mechanism underlying myopia development, and it could be useful in clinical practice to control myopia development in schoolchildren. PURPOSE To model the effect of the crystalline lens on refractive development in schoolchildren. METHODS The Zemax 13 was used to calculate Zernike aberrations and refractions across 50° horizontal visual fields. Optical effects of the anterior chamber depth, lens thickness, and radii of curvature of the lens surfaces on refractions were modeled. Refractive changes induced by lens development in emmetropic and myopic eyes, based on a previous longitudinal study from literature, were calculated. RESULTS A lens thickness reduction with an anterior chamber depth deepening caused a hyperopic shift over the visual fields and even more at the periphery. Opposite effects were found when the lens was thinned without any change of the anterior chamber depth. While a flattening of the anterior lens surface produced hyperopic refractions overall, a posterior lens flattening caused a myopic shift at the periphery, but a hyperopic shift of the central refraction. In the myopic eye, lens development induced refractive change toward more hyperopic over the visual fields and more at the periphery. CONCLUSIONS Lens thinning and lens axial movement participate in peripheral refractive development in schoolchildren, and lens development with a deeper anterior chamber depth and a flatter lens surface in the myopic eye could generate extra hyperopia over visual fields. The myopic lens development could be due to a backward movement of the lens, driven by a backward growth of the ciliary process, which might be a causative factor of myopia development.

Aqueous misdirection syndrome (AMS) is characterized by high intraocular pressure and a shallow anterior chamber because of anterior rotation of the ciliary processes, accumulation of aqueous within the anterior vitreous, and forward displacement of the iris–lens diaphragm (ILD). It mainly occurs in eyes with narrow iridocorneal angles, after intraocular surgery, after laser procedures, or after administration of topical miotics. There is no standardized therapy; however, zonulectomy–hyaloidectomy–anterior vitrectomy seems to be the most effective treatment. A neodymium:YAG (Nd:YAG) laser capsulotomy–hyaloidotomy is a more conservative approach that can decompress the anterior vitreous, release the aqueous, and promote backward displacement of the ILD. We present a case of AMS initially managed with Nd:YAG laser capsulotomy–hyaloidotomy. During this procedure, constriction and redilation of the pupil (ie, the pupil “snapped”) was observed, along with aqueous and vitreous prolapse in the anterior chamber. This sign might represent the moment of aqueous misdirection reversal and could be interpreted by the ophthalmologist as a useful clinical biomarker.

OBJECTIVES To provide in vivo measurements of anterior chamber angle structures and their relationship with age as evaluated by high-frequency ultrasound biomicroscopy (UBM) in patients with primary congenital glaucoma (PCG). METHODS High-frequency UBM was done for 51 PCG eyes from 40 patients (aged from 3 to 96 months) and 11 unaffected contralateral eyes. Parameters, including the proportion of observable abnormal tissue membrane and Schlemm's canal, the largest cross-sectional area (CSA) of Schlemm's canal (SC), SC meridional diameter, trabecular-iris angle (TIA), trabecular meshwork (TM) thickness, iris thickness, ciliary process length, and corneal limbus thickness were compared between the two groups and their relationship with age was explored in PCG eyes. RESULTS Abnormal tissue membrane was detected in 27.5% of PCG eyes and none in unaffected eyes. SC was observed in 73.1% of PGC eyes compared to 100% in unaffected eyes (P

Цель: проведение гистологического исследования цилиарного тела энуклеированного глаза больного, которому ранее прижизненно была выполнена транссклеральная циклофотокоагуляция. Материалы и методы. Проведено гистологическое исследование цилиарного тела энуклеированного глаза после ранее выполненной транссклеральной циклофотокоагуляции по поводу вторичной глаукомы. В ходе исследования материал подразделяли на два образца зона воздействия и интактные участки, служащие контролем. Серийные срезы исследовали с использованием стандартной световой микроскопии. Результаты и обсуждение. В ходе проведения стандартной световой микроскопии при исследовании цилиарного тела повреждения визуализировались как в пигментном эпителии, так и в сосудистом слое. Кроме того, на большом протяжении наблюдалось разрушение эластической пластины, что говорило о значительной протяженности зоны коагуляции. В межмышечном пространстве визуализировались глыбки распыленного пигмента и выраженный отек со скоплением жидкости. Наблюдалось повреждение мышечных волокон цилиарного тела в средних и внутренних слоях. Следовательно, зона рассеивания лазерного излучения при проведении транссклеральной циклофотокоагуляции была очень большая, к тому же воздействие лазера происходило на прилегающие ткани. Кроме того, очаг лазерного воздействия был очень далек от цилиарных отростков. Очевидно, что это была область начала плоской части цилиарного тела. Таким образом, по результатам гистологического исследования можно утверждать, что выполнение транссклеральной циклофотокоагуляции вызывает изменения в прилегающих к области воздействия тканях на довольно большом протяжении, что может вызывать выраженную воспалительную реакцию в послеоперационном периоде. В ходе исследования также было выявлено, что подчас область коагуляции не совпадает с положением цилиарных отростков, то есть воздействие лазера происходит вслепую, что может проявиться недостаточность гипотензивного эффекта от проведенной операции., Purpose: to perform a histological examination of the ciliary body in the enucleated eye of the patient, who had previously undergone intravital transscleral cyclophotocoagulation. Materials and methods. A histological examination of the ciliary body in the enucleated eye was carried out after previously performed transscleral cyclophotocoagulation for secondary glaucoma. During the study, the material was divided into two samples the impact zone and the intact areas that served as control. Serial slices were examined using standard light microscopy. Results and discussion. During examining the ciliary body using a standard light microscopy, injuries were visualized both in the pigment epithelium and the vascular layer. In addition, we observed that the elastic plate was destroyed over a long field, which indicated a significant length of the coagulation zone. In the intermuscular space lumps of sprayed pigment and a pronounced swelling with fluid accumulation were visualized. Damage to the muscle fibers of the ciliary body was observed in the middle and inner layers. Consequently, the area of laser radiation discharge during transscleral cyclophotocoagulation was very large, besides laser affected the adjacent tissues. In addition, the center of laser impact was very far from ciliary processes. It is obvious that this was the area of the beginning of the ciliary bodys flat part. Thus, according to the results of histological examination, it can be stated that the transscleral cyclophotocoagulation causes changes in tissues adjacent to the area of exposure on a fairly large scale, which can cause expressed inflammatory response in the postoperative period. The study also found that sometimes the area of coagulation does not coincide with the position of ciliary processes, that is, laser impact occurs blindly, which may manifest in a lack of hypotensive effect from the operation., №3(60) (2019)

Melatonin is not only synthesized by the pineal gland but by several ocular structures. This natural indoleamine is of great importance for regulating several eye processes, among which pressure homeostasis is included. Glaucoma, the most prevalent eye disease, also known as the silent thief of vision, is a multifactorial pathology that is associated to age and, often, to intraocular hypertension (IOP). Indeed IOP is the only modifiable risk factor and as such medications are available to control it; however, novel medications are sought to minimize undesirable side effects. Melatonin and analogues decrease IOP in both normotensive and hypertensive eyes. Melatonin activates its cognate membrane receptors, MT1 and MT2, which are present in numerous ocular tissues, including the aqueous-humor-producing ciliary processes. Melatonin receptors belong to the superfamily of G-protein-coupled receptors and their activation would lead to different signalling pathways depending on the tissue. This review describes the molecular mechanisms underlying differential functionalities that are attributed to melatonin receptors. Accordingly, the current work highlights the important role of melatonin and its analogues in the healthy and in the glaucomatous eyes, with special attention to the control of intraocular pressure.

Rationale: The amount of aqueous humor that is constantly produced by the ciliary processes and the equal amount that flows out through the trabecular meshwork via the drainage angle or through the uveoscleral route is very small (2–3 μg/min each), representing approximately 1% of the content of the anterior chamber; therefore, it is challenging to visualize its flow. Patient concerns: A 69-year-old man who had high intraocular pressure (IOP) (>20 mm Hg) with the maximum glaucoma eyedrop dose and presented with severe visual field loss (Humphrey Field Analyzer 30–2: –26.32 dB) had been implanted with a 350-mm2 Baerveldt tube of the aqueous chamber type for refractory open-angle glaucoma. The IOP ultimately decreased (

Intraocular pressure (IOP) is maintained as a result of the balance between production of aqueous humour (AH) by the ciliary processes and hydrodynamic resistance to its outflow through the conventional outflow pathway comprising the trabecular meshwork (TM) and Schlemm’s canal (SC). Elevated IOP, which can be caused by increased resistance to AH outflow, is a major risk factor for open-angle glaucoma. Matrix metalloproteinases (MMPs) contribute to conventional aqueous outflow homeostasis in their capacity to remodel extracellular matrices, which has a direct impact on aqueous outflow resistance and IOP. We observed decreased MMP-3 activity in human glaucomatous AH compared to age-matched normotensive control AH. Treatment with glaucomatous AH resulted in significantly increased transendothelial resistance of SC endothelial and TM cell monolayers and reduced monolayer permeability when compared to control AH, or supplemented treatment with exogenous MMP-3. Intracameral inoculation of AAV-2/9 containing a CMV-driven MMP-3 gene (AAV-MMP-3) into wild type mice resulted in efficient transduction of corneal endothelium and an increase in aqueous concentration and activity of MMP-3. Most importantly, AAV-mediated expression of MMP-3 increased outflow facility and decreased IOP, and controlled expression using an inducible promoter activated by topical administration of doxycycline achieved the same effect. Ultrastructural analysis of MMP-3 treated matrices by transmission electron microscopy revealed remodelling and degradation of core extracellular matrix components. These results indicate that periodic induction, via use of an eye drop, of AAV-mediated secretion of MMP-3 into AH could have therapeutic potential for those cases of glaucoma that are sub-optimally responsive to conventional pressure-reducing medications.

In horse, the characterizations of hyalocytes under the steady state are still unclear. Therefore, we investigated characterizations of hyalocytes in normal equine eyes by their immunohistochemical phenotype, histomorphology and distribution. Thirty-one eyes from 18 horses, divided into 4 groups (G) by age, were used: early (G1) and late gestation (G2) fetuses, 1- to 3-year-old (G3) and 8- to 24-year-old (G4) horses. Equine hyalocytes were histologically classified into 4 types, and they immunohistochemically expressed MHC II and CD163. Hyalocytes were detected on and/or around ciliary processes and pars plana in G2, G3 and G4, but were not located on retina and optic papilla. A significant increase in distribution was found between G2 and both G3 and G4, and the largest distribution was found at ciliary processes in these groups. Equine hyalocytes were characterized as residential ocular macrophage and MHC II antigen-bearing cell, accompanied by a pleomorphic appearance and located in the contiguous ciliary body. Our data provided characterizations of hyalocytes in normal equine eyes and may well contribute to improving the understanding of pathogenesis of equine ocular disease.

PURPOSE To describe the anatomic and clinical results of the treatment of severe plateau iris syndrome with lens extraction and endoscopic cycloplasty (ECPL). A secondary aim was to describe 4 novel ultrasound biomicroscopy (UBM) measurements for plateau iris syndrome. DESIGN Prospective case series with UBM evaluation. METHODS Included were 12 eyes of 6 patients with plateau iris refractory to laser iridotomy and iridoplasty, miotic and other glaucoma medical treatment, with appositional angle closure in at least 3 quadrants. Treatment consisted of lens extraction and ECPL, an endoscopic diode laser treatment of the ciliary processes in the superior, nasal, and inferior quadrants. UBM measurements were taken in all quadrants before and after surgery. The untreated temporal quadrants were used as controls. Measurement parameters included: anterior chamber depth (ACD), angle opening distance (AOD 500), trabecular ciliary process distance (TCPD), iris ciliary process distance (ICPD), iris depth (ID), iridocorneal angle (ICA), and sulcus angle (SA). Four novel measurements included: ciliary process thickness (CPT), ciliary process width (CPW), ciliary process area (CPA), and iris ciliary process contact length (ICPCL). Visual acuity, intraocular pressure, glaucoma medications, and complications were also followed. RESULTS The ACD, AOD 500, and ICA all increased significantly (P

OZSAYGILI, CEMAL/0000-0002-8236-1728 WOS: 000456450200002 PubMed ID: 29959631 To investigate whether ocular hypotony formation with 360 degrees endocyclophotocoagulation is possible. Twelve male New Zealand White rabbits were used. Entire ciliary body epithelium was destructed with green laser photocoagulation after pars plana lensectomy and anterior vitrectomy in six rabbits. Endocyclophotocoagulation was not performed to the remaining six rabbits (control group). Intraocular pressure (IOP) was measured preoperatively and followed up everyday in the first week and weekly until the end of month one. All of the rabbits were sacrificed and ciliary bodies were left for gross and light microscopic examination. Mean baseline IOPs were similar in laser and non-laser group (14.8 +/- 1.4 (range 12.2-17.3) vs 14.4 +/- 1.4 (range 12.2-15.9), p=0.650). Mean IOP was 6.6 +/- 0.45mmHg (range 5.9-7.1) in the laser group and 11.5 +/- 1.2mmHg (range 10.2-13.4) in the non-laser group in postoperative day 1. IOP was below 4mmHg in all eyes on the second day and after in laser group. In the macroscopic evaluation, the entire ciliary body had a white (loss of pigmentation) and atrophic appearance in all of the eyes in the laser-treated group compared to non-laser group. In the laser group, light microscopic examination demonstrated a severe 360 degrees disruption of ciliary processes. Ciliary processes were covered with fibrin exudation consisting of fibroblasts. There was a mild inflammation with disruption or atrophy of ciliary body epithelium with cystic vacuolar degeneration. Three hundred sixty degrees endocyclophotocoagulation yielded severe ciliary epithelium damage. IOP reduction started very early and continued in hypotonic levels during follow up period.

The aqueous humour (AH) is a transparent fluid with water-like properties that fills the anterior chamber (AC, the region between the cornea and the iris) and the posterior chamber (PC, the region between the iris and the lens) of the eye, which are connected at the pupil. AH is produced at ciliary processes, and it flows from the PC to the AC, where it is drained in the trabecular meshwork. AH flow is important physiologically, as it governs intraocular pressure and delivers nutrients to avascular ocular tissues. Disruption of AH flow may lead to multiple pathological conditions, such as glaucoma and nutrient depletion. Studying aqueous production, flow and drainage is thus relevant to understand eye physiology and pathophysiology.

Author(s): Moussa, Kareem; Feinstein, Max; Pekmezci, Melike; Lee, Jun Hui; Bloomer, Michele; Oldenburg, Catherine; Sun, Zhimin; Lee, Richard K; Ying, Gui-Shuang; Han, Ying | Abstract: PurposeTo compare the macroscopic and microscopic histologic changes in eyes treated with micropulse transscleral cyclophotocoagulation (MP-TCP) versus continuous wave transscleral cyclophotocoagulation (CW-TCP).MethodsTwelve halves of globes from three pairs of adult cadaveric eyes were randomly assigned to nontreated control, CW-TCP, single MP-TCP treatment, or double MP-TCP treatments, and then sectioned for histologic analysis. Presence or absence of the following four unique histologic changes was recorded: splitting within the ciliary process epithelium (splitting), separation of the pigmented ciliary process epithelium from the stroma (separation), coagulation of collagen and destruction of ciliary process stroma (coagulation), and full-thickness destruction of ciliary process epithelium (destruction).ResultsA total of 498 slides were analyzed, and laser scars in all treated specimens were located in the pars plana. Logistic regression analysis showed that compared with controls, CW-TCP-treated specimens were significantly more likely to experience separation (odds ratio [OR] = 11.1, P = 0.02), coagulation (OR = 24.3, P = 0.002), and destruction (OR = 11.1, P = 0.03). Destruction of the ciliary process epithelium was observed exclusively in CW-TCP-treated sections. No significant differences in histologic features were observed between controls and MP-TCP.ConclusionsMP-TCP does not produce significant histologic changes in cadaveric eyes, whereas CW-TCP treatment does.Translational relevanceThese findings improve understanding of the mechanism of MP-TCP, help explain the increased rates of adverse effects following CW-TCP treatment compared with MP-TCP, and describe effects of MP-TCP at various doses.

Статья представляет собой обзор отечественной и зарубежной литературы по проблеме закрытоугольной глаукомы (ЗУГ) с плоской радужкой, методам ее диагностики и лечения. Было проанализировано более 80 источников отечественной и зарубежной литературы, касающихся проблем диагностики и лечения ЗУГ с плоской радужкой. Отмечены различия в классификации этого заболевания в зарубежной практике, а именно выделение отдельно конфигурации плоской радужки и синдрома плоской радужки, что оказывает влияние на выбор способа лечения. В ходе проведения анализа обзора выявлены особенности диагностики данной формы глаукомы. Подавляющее большинство авторов указывает на наличие средней глубины передней камеры у пациентов с ЗУГ с плоской радужкой. Однако встречаются работы, доказывающие обратное. Также выявлены особенности строения и положения цилиарного тела и его отростков по результатам проведения оптической когерентной томографии переднего сегмента и ультразвуковой биомикроскопии. Что касается методов лечения, то в случае ЗУГ с плоской радужкой назначение медикаментозных гипотензивных препаратов не является терапией выбора. Предпочтение отдается лазерным и хирургическим методам лечения. Однако в настоящее время нет единого мнения о наиболее эффективных и безопасных способах, приводящих к открытию угла передней камеры и стабилизации уровня внутриглазного давления., The article is a review of Russian and foreign literature on the problem of angle-closure glaucoma with a plateau iris, methods of its diagnostics and treatment. More than 80 sources of Russian and foreign literature about the problems of diagnostics and treatment of angle-closure glaucoma (PACG) with a plateau iris were analyzed. There are differences in the classification of this disease in foreign practice, namely the differentiation of plateau iris configuration and plateau iris syndrome, which influences the choice of treatment. The analysis pointed out the specifics of diagnostics of this form of glaucoma. The prevailing majority of authors note that patients with PACG with plateau iris have an average depth of the anterior chamber. However, there are studies that prove the opposite. The review also reveals features of the structure and position of the ciliary body and its processes based on the results of anterior segment optical coherence tomography and ultrasonic biomicroscopy. As for the treatment methods, in case of PACG with a plateau iris, hypotensive medication cannot be considered the therapy of choice. Preference is given to laser and surgical methods of treatment. However, at present, there is no consensus on the most effective and safe methods leading to the anterior chamber angle opening and intraocular pressure level stabilization., №4 (2019)

Myo/Nog cells, named for their expression of MyoD and noggin, enter the eye during early stages of embryonic development. Their release of noggin is critical for normal morphogenesis of the lens and retina. Myo/Nog cells are also present in adult eyes. Single nucleated skeletal muscle cells designated as myofibroblasts arise from Myo/Nog cells in cultures of lens tissue. In this report we document the presence of Myo/Nog cells in the lens, ciliary body and on the zonule of Zinn in mice, rabbits and humans. Myo/Nog cells were rare in all three structures. Their prevalence increased in the lens and ciliary body of rabbits 24 h following cataract surgery. Rabbits developed posterior capsule opacification (PCO) within one month of surgery. The number of Myo/Nog cells continued to be elevated in the lens and ciliary body. Myo/Nog cells containing alpha smooth muscle actin and striated muscle myosin were present on the posterior capsule and overlaid deformations in the capsule. Myo/Nog cells also were present on the zonule fibers and external surface of the posterior capsule. These findings suggest that Myo/Nog contribute to PCO and may use the zonule fibers to migrate between the ciliary processes and lens.

Leukocoria in children should always raise the concern for retinoblastoma. However, a variety of non-neoplastic conditions can also present with leukocoria, including persistent fetal vasculature (PFV), a nonhereditary, congenital anomaly caused by a failure of the fetal intraocular vasculature to regress during development. Classically PFV presents with features that make it easily distinguishable from retinoblastoma, including microphthalmia, retrolental fibrovascular membrane, central dragging of ciliary processes, and cataract. We present an atypical case of PFV in a 9-month-old boy who presented with the unusual features of axial myopia and platyphakia.

For more than a century there has been debate concerning the mechanism of accommodation—whether the lens capsule or lens material itself determines the functional relationship between ciliary muscle contractility and lens deformation during refractive adaptation. This morphological study in monkey eyes investigates the composition and distribution of several connective tissue components in the accommodative apparatus relaying muscle force to lens organization. Elastin distributes on the marginal surface of the ciliary process. A zonule is composed of fibrillin produced by epithelial cells of the process. In the progress of extension over the posterior chamber, fibrils unite into strands and possess longitudinal plasticity. By induction of the elastin network, strands extend in a concentric direction covering the equatorial region of the capsule. Upon tethering to the lens, the strand ramifies into fibrils, penetrating deeply close to the epithelial layer of the lens and binding with the collagen of the intercellular spaces. Tight linkage of the zonule with the capsule transmits precise contractility. Inside the lens, the cortical layer's elastic connective tissue network forms widely spaced lamellae of crystalline fibers. In contrast, the central nuclear lamellae are tightly opposed. The accumulation of lamellae is greater in the anterior cortex than in the posterior, yielding a more variable anterior chamber depth in the visual axis. The plasticity of the zonule and connective tissue distribution inside the lens produces an adjustable configuration. Thus, tight linkage between the dynamism of the capsule with interaction of the lenticular flexibility provides a novel understanding of accommodation. Anat Rec, 298:630–636, 2015.

The authors describe the implantation of the Argus II Retinal Prosthesis System (Argus II) (Second Sight Medical Products, Sylmar, CA) into a short axial length (AL) eye. The authors' main modification is the use of endocyclophotocoagulation (endo-CPC) to the ciliary processes in the area that the cable enters through the sclerotomy. This case describes the surgical technique necessary for successful implantation of the Argus II into a short AL eye. The use of endo-PC prevents chaffing to the ciliary processes, does not affect postoperative intraocular pressure, and facilitates direct visualization of the structures during the surgery, preventing damage during implantation. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:369–371.]

Purpose To determine the relationship of the anatomic position of tissue surrounding the ciliary sulcus using ultrasound biomicroscopy (UBM) for measurement of ciliary sulcus parameters and the surrounding tissue after intracapsular cataract extraction (ICCE) and determine the correct suture site for intraocular lens (IOL) suture fixation. Setting Sugiura Eye Clinic, Asahi General Hospital, Shizouka-ken, Japan. Design Prospective case series. Methods Using UBM, the angle of the ciliary sulcus and several areas of the tissue surrounding the ciliary sulcus were measured from 8 orientations in eyes after ICCE. These measurements and endoscopic observation of the ciliary sulcus indicated the optimum points of needle insertion and needle emergence on the sclera for IOL suture fixation. Endoscopic observation of the ciliary sulcus also showed its shape. Results The shape of the surrounding tissue of the ciliary sulcus was measured in 16 eyes after ICCE, and endoscopy was used to observe the ciliary sulcus during surgery in 150 eyes. For ab interno ciliary sulcus suture fixation, the correct point of needle emergence on the sclera was 2.5 mm from the posterior surgical limbus when a straight needle was used. For ab externo pars plana suture fixation, the correct point of needle insertion on the sclera was 3.0 mm from the posterior surgical limbus. Endoscopic observation showed that the lower surface of the ciliary sulcus was formed by the fusion of neighboring ciliary processes. Conclusion Knowing the detailed shape of ciliary sulcus will allow for more precise IOL suture fixation.

The postnatal evolution of the ciliary processes in the Mongolian gerbil (Meriones unguiculatus) was examined, with particular regard to their morphological organization and to the structural and ultrastructural differentiation of both inner and outer epithelial layers. Gerbil eyes at postnatal (P) 3, 9, 12, 15, 18, 21, and 26 days and at 6 months were fixed with glutaraldehyde 2.5% and examined with the light microscopy on semithin sections and with the transmission electron microscopy. Masked histologists evaluated the samples and performed a morphometric exam on ciliary processes and epithelial cells layers height using the ANOVA test for comparison among groups. From P3 to P15, ciliary processes were formed by rectilinear folds, which progressively elongated at their free extremities. From P18, the processes branched dichotomously and reached their adult zig-zag appearance in cross section at P26. Inner epithelial cells were at first arranged on many layers, then on two layers and, from P15, on a single layer. Outer cells were arranged on a single row from P3. Both cell types showed linear contacts with occasional interdigitations till P9, then complex intercellular junctions. The morphometric analysis demonstrated that while epithelial folds elongated, the ciliary epithelium, and particularly the inner cells, reduced its height. The ciliary processes development of gerbil starts in utero, undergoes significant morphological changes soon after eyelid opening and is completed at P26, when adult organization is reached.

This review describes the most important regions of microcirculation within the eye - their architecture as well as their function. A special emphasis is put on the functional heterogeneity of the microvessels and their role regarding the specific functions localised within the different regions of the eye (e.g. oxygen release by the iris capillaries, production of aqueous humor within the ciliary processes). The microvasculature of choroidea and retina will be described in more detail. The precise adjustment of the blood flow to the functional needs of the inner retina is a very important aspect in the retinal vessels. Here, also pericytes can influence the vessel calibre like in the brain capillaries. Very important is the vascular reaction in general to states of hypoxia, especially to the hypoxic and radical producing states within the photoreceptors. The following reaction of neovascularisation will also be examined. Finally, we describe the metabolic situation of the ganglion cells and nerve fibers leading to and within the optic cup also with regard to glaucoma.