Cell atlas of the human ocular anterior segment: Tissue-specific and shared cell types.

The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens, and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some disorders, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that compose these tissues, we generated an anterior segment cell atlas of the human eye using high-throughput single-nucleus RNA sequencing (snRNAseq). We profiled 195,248 nuclei from nondiseased anterior segment tissues of six human donors, identifying >60 cell types. Many of these cell types were discrete, whereas others, especially in the lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment, revealing that some cell types are unique to a single structure, whereas others are shared across tissues. The integrated cell atlas was then used to investigate cell type-specific expression patterns of more than 900 human ocular disease genes identified through either Mendelian inheritance patterns or genome-wide association studies.

Characterization of lncRNA and mRNA profiles in ciliary body in experimental myopia.

Currently, researchers have mainly focused on the role of the tissues of the posterior segment of the eyes in the development of myopia. However, the ciliary body, an anterior ocular tissue that contracts to initiate the process of accommodation, may also play an important role in the progression of myopia due to the increased demand for near work. In the present study, we established a lens-induced myopia (LIM) animal model in guinea pigs and investigated the molecular changes in the ciliary body associated with the development of myopia based on RNA sequencing. As a result, 871 differentially expressed (DE) mRNAs and 19 DE lncRNAs were identified in the ciliary body between the LIM group and the normal control group. In addition, the lncRNA-mRNA co-expression analysis was performed to explore the target genes of lncRNAs, which were mainly enriched in the Rap1 signaling pathway, cytokine-cytokine receptor interaction, and complement and coagulation cascades pathways based on the functional enrichment analysis. Among the target genes of lncRNAs, three hub genes, including Ctnnb1, Pik3r1, and Itgb1, were found to be involved in the Rap1 signaling pathway. Interestingly, two crucial genes, Grk1 and Pde6a, which are mainly expressed in retinal photoreceptors, were enriched in visual perception in the ciliary body in functional analysis and were verified to be expressed in the ciliary body. These findings indicate the molecular pathogenetic role of the ciliary body in myopia and provide new insights into the underlying mechanism of myopia development. Further studies are needed to explore the specific contributions of these identified lncRNAs and mRNAs to the development of myopia.

Intraocular pressure across the lifespan of Tg-MYOCY437H mice.

Transgenic C57BL/6 mice expressing human myocilinY437 (Tg-MYOCY437H) are a well-established model for primary open-angle glaucoma (POAG). While the reduced trabecular meshwork (TM) cellularity due to severe endoplasmic reticulum (ER) stress has been characterized as the etiology of this model, there is a limited understanding of how glaucomatous phenotypes evolve over the lifespan of Tg-MyocY437H mice. In this study, we compiled the model's intraocular pressure (IOP) data recorded in our laboratory from 2017 to 2023 and selected representative eyes to measure the outflow facility (Cr), a critical parameter indicating the condition of the conventional TM pathway. We found that Tg-MYOCY437H mice aged 4-12 months exhibited significantly higher IOPs than age-matched C57BL/6 mice. Notably, a decline in IOP was observed in Tg-MYOCY437H mice at 17-24 months of age, a phenomenon not attributable to the gene dosage of mutant myocilin. Measurements of the Cr of Tg-MYOCY437H mice indicated that the age-related IOP reduction was not a result of ongoing TM damage. Instead, Hematoxylin and Eosin staining, immunohistochemistry analysis, and transmission electron microscopic examination revealed that this reduction might be induced by degenerations of the non-pigmented epithelium in the ciliary body of aged Tg-MYOCY437H mice. Overall, our findings provide a comprehensive profile of mutant myocilin-induced ocular changes over the Tg-MYOCY437H mouse lifespan and suggest a specific temporal window of elevated IOP that may be ideal for experimental purposes.

Ciliary body myxoid epithelioid sarcoma in a cat: a case report.

BACKGROUND: The majority of primary, intraocular tumors in cats originate from the uvea and include feline diffuse iris melanoma, lymphoma, and iridociliary epithelial adenoma or adenocarcinoma. In this case report, we describe for the first time the clinical, histological, and immunohistochemical findings of a rare myxoid intraocular neoplasm arising from the ciliary body in a cat. CASE PRESENTATION: A 14-year-old, female, spayed domestic shorthaired cat was presented for evaluation of discolouration of the right eye. Upon examination, a clear to light whitish-tan, bubble-shaped intraocular mass adherent to the inferior ciliary body and extending into the anterior chamber was noted. Within five weeks, the tumor was significantly larger and the eye had developed secondary glaucoma so was enucleated. Light microscopic examination of the globe revealed a multinodular, hypocellular neoplasm arising from the ciliary body composed of interwoven spindle cells embedded in abundant amounts of a lightly basophilic myxoid matrix. Neoplastic cells exhibited strong immunoreactivity for cytokeratin while also showing moderate to strong immunoreactivity to vimentin. A diagnosis was therefore made of an unusual intraocular myxoid epithelioid sarcoma arising from the ciliary body. CONCLUSIONS: Although apparently exceedingly rare, epithelioid myxosarcoma should be included as a differential diagnosis for intraocular tumors in cats and they represent a clinical, histologic, and immunohistochemical diagnostic challenge. Early surgical intervention should be considered to prevent local invasion and ascension to the brain.

Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

A rare case of bilateral malignant glaucoma after cataract surgery with capsular tension ring implantation: a case report.

BACKGROUND: Bilateral malignant glaucoma induced by a capsular tension ring associated with ring-shaped cysts of the ciliary body post-cataract surgery is rare. Herein, we present a case to highlight the possibility of capsular tension ring-induced malignant glaucoma. CASE PRESENTATION: A 59-year-old woman underwent phacoemulsification combined with capsular tension ring implantation for cataracts and zonular fibre laxity in both eyes. Upon admission, annular ciliary masses were detected in both eyes using ultrasound biomicroscopy. Two months post-surgery, the patient experienced vision deterioration, high intraocular pressure, and an axial shallowing anterior chamber in the right eye, and responded poorly to traditional anti-glaucoma medication. Ten days later, similar symptoms appeared in the left eye. Ultrasound biomicroscopy detected contact between the ciliary body and the capsular tension ring. Subsequently, malignant glaucoma was diagnosed. Anterior and posterior capsulotomies performed peripheral to intraocular lens optics using neodymium: YAG laser restored communication and alleviated the symptoms. A one-year follow-up revealed stable intraocular pressure and anterior chamber in both eyes. CONCLUSIONS: This is the first case report of bilateral malignant glaucoma after cataract surgery induced by capsular tension ring, which is associated with bilateral ring-shaped cysts of the ciliary body. Blockage between the ciliary body and capsular tension ring was confirmed using ultrasound biomicroscopy.

Tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment: a case report.

BACKGROUND: Ocular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment. CASE REPORT: A 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved. CONCLUSIONS: Tuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis.

Settings and effectiveness of the revised probe compared to the original probe for micropulse transscleral cyclophotocoagulation.

PURPOSE: The goal of this study was to compare the settings and effectiveness of the original P3 and revised P3 probes for micropulse transscleral cyclophotocoagulation. METHODS: This retrospective cross sectional study includes a total of 56 patients with glaucoma who received micropulse transscleral cyclophotocoagulation. 32 patients received treatment with the original P3 probe and 24 received treatment with the revised P3 probe. Success was defined as a 20% reduction in intraocular pressure. Laser settings, pre-op and post-op intraocular pressures, and pre-op and post-op medications were assessed. RESULTS: A 20% IOP reduction was achieved in 50% of patients in the original probe vs. 58.3% in the revised probe at one month (P = 0.536) and 71.9% vs. 50% at three months (P = 0.094), respectively. The revised P3 probe used higher values of power (2500 mW vs. 2023 mW, P < 0.0001), total duration (217 s vs. 179 s, P < 0.0001), and energy (170 J vs. 113 J, P < 0.001). There was a significant decrease in IOP lowering meds with the original probe at one month (-0.9 +/- 1.5 vs. -0.0 +/- 0.7, P = 0.010), but this was not seen at three months. CONCLUSIONS: There is no significant difference in IOP lowering effect between probes despite the revised probe using higher total energy. The original probe may be associated with fewer medications at 1 month, but not at 3 months. Further studies with longer follow up are needed to optimize the treatment parameters in order to maximize effectiveness while limiting side effects.

Concurrent ciliary body detachment in patients presenting with serous choroidal detachment following glaucoma surgery.

PURPOSE: To examine the rate of ciliary body detachment in patients with choroidal detachment following glaucoma surgery and its effect on the clinical course, management, and prognosis. METHODS: A prospective observational case-series study. Patients with choroidal detachment following glaucoma surgery in 2018-2019 were included. All underwent complete ophthalmological examination and ultrasound biomicroscopy for evaluation of the presence and extent of ciliary body detachment. Follow-up examinations including ultrasound biomicroscopy scans were performed at 1 week, 1 month, 3 months, and 6 months. RESULTS: Eight patients (8 eyes) were enrolled, 4 male and 4 female, of mean age 72 years (range 60-83). Five patients underwent trabeculectomy with mitomycin C (0.02%), which was combined with phacoemulsification cataract extraction in one; two underwent Ahmed glaucoma valve implantations, and one underwent ab-interno Xen45 gel stent implantation with mitomycin C (0.02%). The mean intraocular pressure was 26.0 ± 7.65 mmHg preoperatively, dropping to 6.9 ± 2.64 mmHg on first postoperative day one. Mean time from surgery to diagnosis of choroidal detachment was 11.6 ± 5.73 days. Ciliary body detachment was identified by ultrasound biomicroscopy in all patients, ranging between one and four quadrants. All patients were treated with topical steroids and cycloplegics; three (37.5%) received oral steroids. No surgical intervention for the choroidal or ciliary body detachments was indicated. CONCLUSIONS: In this real-world prospective study, concurrent ciliary body detachment was identified in all patients who presented with choroidal detachment following glaucoma surgery. This observation may deepen our understanding of the mechanism underlying the hypotony that is often seen after glaucoma surgery.

Evaluation of ciliary body cysts in candidates for phakic lens implantation.

PURPOSE: Phakic lens implantation in the ciliary sulcus of the eye can be complicated by coincident ciliary body cysts (CBC). We developed an ultrasound imaging and mapping protocol for these cysts. METHODS: This is a retrospective case series of all patients who underwent ICL workup at a single institution from April 2015 to October 2019. A standardized ultrasound biomicroscopy (UBM) imaging protocol was developed to screen for CBCs in either the ciliary body or sulcus. The locations and dimensions of all CBCs were graphically represented. RESULTS: The prevalence of CBCs in 158 patients undergoing ICL workup was 34.8%. Among the 159 CBCs detected in 55 patients, 83 were in the sulcus (52%) and 76 were restricted to the ciliary body (48%). ICLs were implanted in 40 eyes with CBCs and 3 eyes with CBCs located within the sulcus horizontally required ICL repositioning due to ICL rotation or iris chafing. CONCLUSION: CBCs were incidentally found in 34.8% of patients undergoing ICL workup. ICL implantation was complicated in 3 of the eyes with CBCs in the horizontal sulcus. Although CBCs are not an absolute contraindication for ICL surgery, we recommend preoperative UBM screening of the ciliary sulcus.

[Comparative evaluation of transscleral laser exposure in anatomical experiment]. / Sravnitel'naya otsenka lazernogo transskleral'nogo vozdeistviya v usloviyakh anatomicheskogo eksperimenta.

PURPOSE: This study comparatively analyzed the morphology of eye tissues after laser exposure using the latest generation of transscleral laser techniques - micropulse transscleral cyclophotocoagulation (MP-TSCPC) and laser activation of scleral hydropermeability (LASH) - in an anatomical experiment. MATERIAL AND METHODS: The study used pulsed-periodic radiation of an Er-glass fiber laser (λ=1.56 µm) and radiation of a diode laser (λ=0.81 µm) in the micropulse mode. A comparative morphological evaluation of histological preparations of target scleral and ciliary body (CB) tissues was performed with the study of laser-induced changes occurring after LASH and MP-TSCPC. RESULTS: The study of histological preparations obtained after MP-TSCPC and LASH did not reveal any noticeable signs of an inflammatory reaction or significant destructive changes. There were no signs of pronounced coagulative changes in the form of disorganization of connective and muscle tissue in the exposure area. At the same time, MP-TSCPC was accompanied by thinning and discontinuity of the CB pigment epithelium in the projection of its flat part and expansion of the gaps between the anterior connective tissue fibers fixing the CB to the sclera, which is likely a factor contributing to uveoscleral outflow. After LASH, in the irradiated areas at the level of the outer layers of the sclera (¾ of its thickness) located in the projection of the flat part of the ciliary body, multiple slit-like cavities and enlargements (stretching) of interfiber spaces were revealed with simultaneous compaction of the inner part of the sclera (» of its thickness). CONCLUSION: The identified morphological changes may indicate certain differences in the mechanisms of intraocular pressure (IOP) reduction after MP-TSCPC and LASH. The results of this study suggest that the enhancement of uveoscleral outflow of intraocular fluid and the hypotensive effect after MP-TSCPC may be associated with laser-induced expansion of the interspaces between the anterior connective tissue fibers of the CB in the suprachoroidal space. With LASH, the possible mechanism of lowering IOP may be related rather to an increase in transscleral filtration due to the appearance of slit-like interfiber spaces in the sclera, caused by local contraction of scleral fibers in the area of laser exposure. The absence of pronounced destructive changes at the histological level indicates the gentle nature of both laser techniques and the possibility of expanding the indications for the use of LASH in the treatment of glaucoma, including at its earlier stages.

The evolution of mechanism of accommodation and a novel hypothesis.

Myopia and presbyopia are two major optometry problems facing the whole society. The mechanism of accommodation is strongly related to the treatments of myopia and presbyopia. However, the key mechanism of accommodation has puzzled us for over 400 years and is still not clear at present, leading to the stagnation of prevention and treatment of myopia and presbyopia. With the continued development of experimental technologies and equipment, the approaches to elucidate accommodation's intricacies have become more methodological and sophisticated. Fortunately, some significant progress has been made. This article is to review the evolution of the mechanism of accommodation. Helmholtz proposed a classical theory of "zonules relax during accommodation." In contrast, Schachar put forward a theory of "zonules taut during accommodation." Those hypotheses are relatively complete, but either do not fully explain everything about the accommodation mechanism or lack sufficient experimental and clinical evidence to support them. Then, some contentious issues are discussed in detail to find the truth. Finally, we proposed our hypothesis about accommodation based on the anatomy of the accommodative apparatus.

Impact of accommodative insufficiency and accommodative/vergence therapy on ciliary muscle thickness in the eye.

PURPOSE: Recent evidence suggests that the ciliary muscle apical fibres are most responsive to accommodative load; however, the structure of the ciliary muscle in individuals with accommodative insufficiency is unknown. This study examined ciliary muscle structure in individuals with accommodative insufficiency (AI). We also determined the response of the ciliary muscle to accommodative/vergence therapy and increasing accommodative demands to investigate the muscle's responsiveness to workload. METHODS: Subjects with AI were enrolled and matched by age and refractive error with subjects enrolled in another ciliary muscle study as controls. Anterior segment optical coherence tomography was used to measure the ciliary muscle thickness (CMT) at rest (0D), maximum thickness (CMTMAX) and over the area from 0.75 mm (CMT0.75) to 3 mm (CMT3) posterior to the scleral spur of the right eye. For those with AI, the ciliary muscle was also measured at increasing levels of accommodative demand (2D, 4D and 6D), both before and after accommodative/vergence therapy. RESULTS: Sixteen subjects with AI (mean age = 17.4 years, SD = 8.0) were matched with 48 controls (mean age = 17.8 years, SD = 8.2). On average, the controls had 52-72 µm thicker ciliary muscles in the apical region at 0D than those with AI (p = 0.03 for both CMTMAX and CMT 0.75). Differences in thickness between the groups in other regions of the muscle were not statistically significant. After 8 weeks of accommodative/vergence therapy, the CMT increased by an average of 22-42 µm (p ≤ 0.04 for all), while AA increased by 7D (p < 0.001). CONCLUSIONS: This study demonstrated significantly thinner apical ciliary muscle thickness in those with AI and that the ciliary muscle can thicken in response to increased workload. This may explain the mechanism for improvement in signs and symptoms with accommodative/vergence therapy.

Factors defining the intraocular pressure-lowering effect of phacoemulsification and laser peripheral iridotomy in patients with primary angle closure : Factors defining IOP lowering effect of PE and LPI in PAC.

To identify whether gonioscopic ciliary body visibility and factors including anterior chamber depth (ACD), axial length (AL), acute attack history, and preoperative intraocular pressure (IOP) had any effect on IOP decrease in primary angle closure (PAC) and primary angle-closure glaucoma (PACG) after phacoemulsification (PE) and/or laser peripheral iridotomy (LPI). This retrospective-design study was conducted with 81 eyes with PAC and PACG; 33 eyes whose IOP was controlled with LPI and PE constituted group 1, and 48 eyes whose IOP was controlled using LPI alone comprised group 2. The effects on preoperative and last-visit IOP levels, ciliary body visibility, ACD, AL, and acute attacks were analyzed. Eyes within the groups were similar in AL, ACD, and preoperative IOP except for acute attack history, which was found to be higher in group 1. For group 1, none of the factors was found to have a differentiative effect on IOP decrease after PE, except eyes with preoperative IOP > 21 mm Hg, which had significantly more IOP reduction. For group 2, no difference was found in ciliary body visibility, and higher or lower ACD. However, eyes with AL ≥ 22 mm, positive acute attack history, and higher preoperative IOP were associated with significantly better IOP reduction. We found no relationship between ciliary body visibility and an IOP-reducing effect of PE and LPI. Although we found PE effective in IOP reduction in all eyes, we determined LPI to have a lesser IOP-reducing effect in eyes with IOP ≤ 21 mm Hg and AL < 22 mm.

[Adenocarcinoma of nonpigmented ciliary body epithelium (clinical cases)]. / Adenokartsinoma iz bespigmentnogo epiteliya tsiliarnogo tela (klinicheskie nablyudeniya).

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

[Morphological evaluation of the results of laser activation of scleral hydropermeability in the treatment of glaucoma]. / Morfologicheskaya otsenka rezul'tatov operatsii lazernoi aktivatsii gidropronitsaemosti sklery v lechenii glaukomy.

PURPOSE: The study attempted to experimentally substantiate the possibility of using the laser activation of scleral hydropermeability (LASH) technique in glaucoma treatment by morphological evaluation of treatment outcomes. MATERIAL AND METHODS: The pulsed-periodic radiation from an Er-glass fiber laser (λ=1.56 µm) was used. The model experiment consisted of evaluating ultrafiltration of fluid through the tissues of human sclera autopsy specimen according to the original technique using neodymium chloride-based labeling agent and scanning electron microscopy. The clinical part of the study consisted of optical coherence tomography (OCT) and laser confocal microscopy of the sclera and conjunctiva (CMSC) performed in vivo immediately after laser treatment in the laser application sites in 5 patients (5 eyes) aged 57 to 68 years with uncompensated advanced (IIIb-c) stage of glaucoma who had previously underwent LASH surgery. RESULTS: Results of morphological evaluation after LASH revealed structural changes indicating increased transscleral ultrafiltration: increased intrastromal hyporeflective areas in the sclera, thinning of collagen fibers, formation of porous structures. Using an original technique involving neodymium chloride-based labeling agent and scanning electron microscopy, we were able to prove the enhancement of transscleral ultrafiltration. The results of the experiment were confirmed by in vivo OCT images of the sclera and CMSC performed in 5 patients with advanced glaucoma after LASH surgery, in which tissue decompaction in the laser-exposed areas was clearly visualized. CONCLUSION: The revealed structural changes indicate the possibility of reducing intraocular pressure after LASH by the means of forming scleral porous structures and increasing transscleral ultrafiltration. Experimentally selected optimal mode of laser exposure (0.66 W with total exposure time of 6 seconds) during LASH helps avoid gross destructive changes in the eye tissues, making the proposed intervention a sparing approach to the treatment of glaucoma.

[Clinical outcomes of laser activation of hydraulic permeability of the sclera in the treatment of advanced glaucoma]. / Klinicheskie rezul'taty lazernoi aktivatsii gidropronitsaemosti sklery v lechenii patsientov s dalekozashedshei stadiei glaukomy.

PURPOSE: This study evaluates the hypotensive effect and the outcomes of intravital morphological changes in the intervention site after laser activation of scleral hydro-permeability (LASH) by pulsed-periodic radiation from an Er-glass fiber laser (λ=1.56 µm) in patients with advanced glaucoma. MATERIAL AND METHODS: LASH surgery was performed in 19 patients (19 eyes) aged 48 to 73 years with uncompensated advanced stage (IIIb-c) glaucoma. In addition to standard methods of investigation, all patients were examined with optical coherence tomography (OCT) and laser confocal microscopy of sclera and conjunctiva (CMSC) at the laser treatment sites, and electronic tonography. RESULTS: The hypotensive effect after LASH in patients with advanced glaucoma was observed in 94.7% (n=18) of cases. The decrease in intraocular pressure (IOP) averaged 24.4% from baseline one month after intervention and 32.96% after six months of follow-up. In 15.7% (n=3) of cases, the recorded IOP decrease was insufficient as its target values were not achieved. However, in the vast majority of patients (n=16), the recorded IOP decrease corresponded to the target values and indicated compensation of the process. Results of complex morphological evaluation after LASH revealed structural changes indirectly indicating possible laser-induced influence on the processes of increased transscleral filtration and uveoscleral outflow. A high positive correlation dependence (r=0.848) was also revealed between the degree of IOP lowering and the increase in the coefficient of ease of aqueous humor outflow, attesting to the fact that IOP lowering was mainly due to the improvement of intraocular fluid outflow. CONCLUSION: The demonstrated efficacy of LASH technology indicates the possibility of its successful application as an independent method of IOP reduction in patients with advanced glaucoma.

Iris and Ciliary Body Melanocytomas Are Defined by Solitary GNAQ Mutation Without Additional Oncogenic Alterations.

OBJECTIVE: To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication. DESIGN: Retrospective case-control study. SUBJECTS: Patients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea. METHODS: Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features. MAIN OUTCOME MEASURES: Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence. RESULTS: Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized. CONCLUSIONS: In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions.

Ocular proteomic and transcriptomic changes with aging in a rabbit model of lensectomy with intraocular lens insertion.

Children that undergo intraocular surgery have an exaggerated postoperative response compared to adults that can result in significant postoperative challenges and reduced post-operative visual acuity. Rabbits were used as an animal model for investigating aging differences, treatment options, and surgical techniques for anterior chamber surgical interventions due to similarities in anterior chamber size and decreasing postoperative response with age. In our study, juvenile and adult rabbits underwent lensectomy with intraocular lens (IOL) insertion to determine how ocular RNA transcripts and proteins change with age. Rabbits underwent lensectomy with IOL insertion, and aqueous humor (AH) was collected immediately prior to surgery and at the peak of the postoperative response on post-operative day 3. Proteins related to coagulation and inflammation were assessed using targeted mass spectrometry. In addition, the cornea and iris/ciliary body tissues were dissected, and transcripts analyzed using RNA sequencing. While clinically, juvenile rabbits have greater fibrin formation following intraocular surgery compared to older rabbits, this change does not appear to be related to relative abundance levels of coagulation and inflammatory proteins in the AH. Gene transcript levels from a variety of immune response and inflammatory pathways reflected significant increases when comparing operated to unoperated ocular tissues, indicating the significant impact that surgery has on each ocular structure. This work further advances our understanding of how the rabbit eye proteomic and transcriptomic changes in response to surgery with aging, as we seek to ultimately identify the mechanisms for the exaggerated postoperative responses after pediatric intraocular surgery.

The mounted alloimmunity of the iris-ciliary body devotes a hotbed of immune cells for corneal transplantation rejection.

Graft rejection is still the major obstacle causing corneal transplantation failure. However, the underlying pathogenesis remains largely unclear. The iris-ciliary body (I-C) is enriched with blood vessels and various immune cell populations, presumably predisposed to be involved in corneal transplantation rejection. After penetrating keratoplasty, compared to the normal (Nor) and syngeneic (Syn) groups, I-C tissues in the allogeneic (Allo) group displayed stronger alloimmune responses, with more infiltrations of CD45+ inflammatory cells and CD3+ lymphocytes, increased transcriptional levels of pro-inflammatory cytokines, and elevated NF-κB activity. This histopathology was similar to the pathological alterations of corneal allografts. Angiography analysis revealed the abnormal vasculature in the iris during allograft rejection, characterized by vasodilatation, increased vessel density, and vascular permeability. While, immunofluorescence staining showed the intact tight junction of the posterior iris epithelium. In vitro, human microvascular endothelial cells (HMECs) stimulated by tumor necrosis factor-α (TNF-α) showed an increased Evans blue (EB)-albumin leakage, with lower expression of zonula occludens-1 (ZO-1) and Occludin. The increased EB-albumin leakage, up-regulated NF-κB activity, and reduced expression of ZO-1 and Occludin could be partially reversed after cyclosporine A (CsA) administration. In contrast, the barrier function in primary mouse iris pigment epithelial cells (IPEs) after TNF-α treatment remained largely unchanged. These findings revealed the vigorous alloimmunity in I-C tissues, characterized with impaired vascularization but intact posterior epithelial barrier in the iris, which allowed proteins and immune cells to be exudated from the front surface of I-C tissues, and facilitated immune reaction in the anterior chamber, thereby contributing to aggravated corneal transplantation rejection.