Bestrophin-2 and glutamine synthetase form a complex for glutamate release.

Bestrophin-2 (BEST2) is a member of the bestrophin family of calcium-activated anion channels that has a critical role in ocular physiology1-4. Here we uncover a directional permeability of BEST2 to glutamate that heavily favours glutamate exit, identify glutamine synthetase (GS) as a binding partner of BEST2 in the ciliary body of the eye, and solve the structure of the BEST2-GS complex. BEST2 reduces cytosolic GS activity by tethering GS to the cell membrane. GS extends the ion conducting pathway of BEST2 through its central cavity and inhibits BEST2 channel function in the absence of intracellular glutamate, but sensitizes BEST2 to intracellular glutamate, which promotes the opening of BEST2 and thus relieves the inhibitory effect of GS. We demonstrate the physiological role of BEST2 in conducting chloride and glutamate and the influence of GS in non-pigmented ciliary epithelial cells. Together, our results reveal a novel mechanism of glutamate release through BEST2-GS.

Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye.

Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.

Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis.

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.

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.

A digoxin derivative that potently reduces intraocular pressure: efficacy and mechanism of action in different animal models.

Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human α2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the α2 isoform of Na,K-ATPase, which is expressed strongly in nonpigmented cells, reducing aqueous humor (AH) inflow. This paper extends assessment of efficacy and mechanism of action of DcB using an ocular hypertensive nonhuman primate model (OHT-NHP) (Macaca fascicularis). In OHT-NHP, DcB potently lowers IOP, in both acute (24 h) and extended (7-10 days) settings, accompanied by increased aqueous humor flow rate (AFR). By contrast, ocular normotensive animals (ONT-NHP) are poorly responsive to DcB, if at all. The mechanism of action of DcB has been analyzed using isolated porcine ciliary epithelium and perfused enucleated eyes to study AH inflow and AH outflow facility, respectively. 1) DcB significantly stimulates AH inflow although prior addition of 8-Br-cAMP, which raises AH inflow, precludes additional effects of DcB. 2) DcB significantly increases AH outflow facility via the trabecular meshwork (TM). Taken together, the data indicate that the original hypothesis on the mechanism of action must be revised. In the OHT-NHP, and presumably other species, DcB lowers IOP by increasing AH outflow facility rather than by decreasing AH inflow.NEW & NOTEWORTHY When applied topically, a cyclobutyl derivative of digoxin (DcB) potently reduces intraocular pressure in an ocular hypertensive nonhuman primate model (Macaca fascicularis), associated with increased aqueous humor (AH) flow rate (AFR). The mechanism of action of DcB involves increased AH outflow facility as detected in enucleated perfused porcine eyes and, in parallel, increased (AH) inflow as detected in isolated porcine ciliary epithelium. DcB might have potential as a drug for the treatment of open-angle human glaucoma.

Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses.

PURPOSE: The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume. DESIGN: Retrospective, multicenter case series of patients with uveal melanoma involving the choroid, ciliary body, or both. PARTICIPANTS: Six thousand five hundred twenty-eight consecutively registered patients treated at 3 tertiary ocular oncology centers on 2 continents between 1981 and 2022. METHODS: Data on survival, tumor size, and extent were collected for all 6528 patients. Tumor volume was estimated using a simple equation based on largest basal diameter and thickness. Volume-based size categories and stages were developed and validated in independent patient cohorts using competing risk analyses, and correlations with cytogenetic and cytomorphologic features were examined. MAIN OUTCOME MEASURE: Cumulative incidence of metastatic death. RESULTS: The 6528 patients were distributed over 7 stages based on estimated tumor volume and anatomic extent (V stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), with a 15-year incidence of metastatic death ranging from 7% to 77%. A new category, V1min, and corresponding stage IA, were introduced, indicating an excellent prognosis. Metastatic mortality in V stage IIIC was significantly higher than that in V stage IIIB (P = 0.03), whereas incidence curves crossed for patients in AJCC stages IIIC vs. IIIB (P = 0.53). Univariable and multivariable competing risk regressions demonstrated higher Wald statistics for V stages compared with AJCC stages (1152 vs. 1038 and 71 vs. 17, respectively). The frequency of monosomy 3, gain of chromosome 8q, and epithelioid cytomorphologic features increased with tumor volume (R2 = 0.70, R2 = 0.50, and R2 = 0.71, respectively; P < 0.001) and showed similar correlations with both AJCC and V stages. CONCLUSIONS: Anatomic classification and staging of ciliary body and choroidal melanomas based on estimation of tumor volume improves prognostication of metastatic mortality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The ocular immunological alterations in the process of high-risk corneal transplantation rejection.

PURPOSE: This study aims to reveal the immunopathogenesis of the high-risk corneal transplantation using a comparative proteomic approach. METHODS: The immunological properties of ocular tissues (including corneal grafts, aqueous humour, and iris-ciliary body) were analysed using a high-risk rabbit corneal transplantation model employing a comparative proteomic approach. RESULTS: The corneal grafts revealed a dramatic increase in the immune response both at the early (postoperative day 7) and rejection stages, along with the appearance of transplantation stress-induced cellular senescence in the early stage. The aqueous humour (AH) displayed persistent pathological alterations, indicated by the significant enrichment of complement and coagulation cascades pathway in the early stage and interleukin (IL)-17 signalling pathway in the rejection stage. More surprisingly, the pronounced elevation of immune response was also observed in the iris-ciliary body (I-CB) tissues at the early and rejection stages. The enriched immune-related pathways were associated with antigen processing and presentation, complement and coagulation cascades, and IL-17 signalling pathway. Furthermore, proteomic analysis revealed that the implantation of Cyclosporine A drug delivery system (CsA-DDS) into the anterior chamber obviously mitigated corneal transplantation rejection by inhibiting immunoreaction both in the corneal grafts and I-CB tissues. CONCLUSION: The results highlighted the involvement of intraocular immunity both in the grafts and I-CB tissues during corneal transplantation rejection, further suggesting the anterior chamber as an optimal drug-delivery site for its treatment.

Aqueous humor as eye lymph: A crossroad between venous and lymphatic system.

Aqueous humor (AQH) is a transparent fluid with characteristics similar to those of the interstitial fluid, which fills the eyeball posterior and anterior chambers and circulates in them from the sites of production to those of drainage. The AQH volume and pressure homeostasis is essential for the trophism of the ocular avascular tissues and their normal structure and function. Different AQH outflow pathways exist, including a main pathway, quite well defined anatomically and referred to as the conventional pathway, and some accessory pathways, more recently described and still not fully morphofunctionally understood, generically referred to as unconventional pathways. The conventional pathway is based on the existence of a series of conduits starting with the trabecular meshwork and Schlemm's Canal and continuing with a system of intrascleral and episcleral venules, which are tributaries to veins of the anterior segment of the eyeball. The unconventional pathways are mainly represented by the uveoscleral pathway, in which AQH flows through clefts, interstitial conduits located in the ciliary body and sclera, and then merges into the aforementioned intrascleral and episcleral venules. A further unconventional pathway, the lymphatic pathway, has been supported by the demonstration of lymphatic microvessels in the limbal sclera and, possibly, in the uvea (ciliary body, choroid) as well as by the ocular glymphatic channels, present in the neural retina and optic nerve. It follows that AQH may be drained from the eyeball through blood vessels (TM-SC pathway, US pathway) or lymphatic vessels (lymphatic pathway), and the different pathways may integrate or compensate for each other, optimizing the AQH drainage. The present review aims to define the state-of-the-art concerning the structural organization and the functional anatomy of all the AQH outflow pathways. Particular attention is paid to examining the regulatory mechanisms active in each of them. The new data on the anatomy and physiology of AQH outflow pathways is the key to understanding the pathophysiology of AQH outflow disorders and could open the way for novel approaches to their treatment.

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.

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.

TRPP2 is located in the primary cilia of human non-pigmented ciliary epithelial cells.

PURPOSE: Mechanosensitive channels (MSCs) and primary cilium possess a possible relevance for the sensation of intraocular pressure (IOP). However, there is only limited data on their expression and localization in the ciliary body epithelium (CBE). The purpose of this study was to characterize the expression and localization of TRPP2 in a human non-pigmented ciliary epithelial cell (HNPCE) line. METHODS: The expression of the TRPP2 was studied by quantitative (q)RT-PCR and in situ hybridization in rat and human tissue. Protein expression and distribution were studied by western blot analysis, immunohistochemistry, and immunoelectron microscopy. Cellular location of TRPP2 was determined in rat and human CBE by immunofluorescence and immunoblot analysis. Electron microscopy studies were conducted to evaluate where and with substructure TRPP2 is localized in the HNPCE cell line. RESULTS: The expression of TRPP2 in rat and human non-pigmented ciliary epithelium was detected. TRPP2 was mainly located in nuclei, but also showed a punctate distribution pattern in the cytoplasm of HNPCE of the tissue and the cell line. In HNPCE cell culture, primary cilia did exhibit different length following serum starvation and hydrostatic pressure. TRPP2 was found to be colocalized with these cilia in HNPCE cells. CONCLUSION: The expression of TRPP2 and the primary cilium in the CB may indicate a possible role, such as the sensing of hydrostatic pressure, for the regulation of IOP. Functional studies via patch clamp or pharmacological intervention have yet to clarify the relevance for the physiological situation or aqueous humor regulation.

The correlation of anterior segment structures in primary congenital glaucoma by ultrasound biomicroscopy with disease severity and surgical outcomes.

PURPOSE: To evaluate the anterior segment structures using ultrasound biomicroscopy (UBM) in primary congenital glaucoma (PCG) and explore their correlation with disease severity and surgical outcomes. METHODS: Clinical information of PCG patients who underwent UBM prior to their first glaucoma surgeries from September 2014 to March 2021 were reviewed. The study included 214 UBM images of 154 PCG eyes and 60 fellow unaffected eyes. Anterior segment characteristics were analyzed. UBM parameters, including the iris thickness (IT) at variant distances from the pupil edge and iris root, anterior chamber depth (ACD), and pupil diameter (PD), were compared between two groups and their relationship with clinical factors and surgical outcomes were analyzed in PCG eyes. RESULTS: PCG eyes had unclear scleral spur, thin iris, wide anterior chamber angle, deep anterior chamber, rarefied ciliary body, elongated ciliary processes, and abnormal anterior iris insertion. ITs were thinner, ACD was deeper, and PD was larger in PCG eyes than fellow unaffected eyes (all P < 0.001). In PCG eyes, thinner ITs correlated with bilateral involvement and earlier age at presentation, and larger PD correlated with earlier age at presentation (P = 0.030) and higher intraocular pressure (P < 0.001). Thinner IT2 (P = 0.046) and larger PD (P = 0.049) were identified as risk factors for surgical failure. CONCLUSION: UBM is a powerful technique to exam anterior segment structures in PCG. The anatomical features are associated with disease severity and surgical outcomes, providing essential clinical insights.

Lens height paraments comparison according to ciliary sulcus width (CSW): a pilot study of the predictive role of CLR and STSL for vault after ICL implantation.

BACKGROUND: To assess the relationship between postoperative implantable collamer lens (ICL) vault and lens height obtained from two different measurements. METHODS: A retrospective case series study enrolled eyes with horizontally implanted ICL. Crystal lens rise (CLR) and the distance between STS plane and anterior crystalline lens surface (STSL) were measured in the horizontal and vertical directions using ultrasound biomicroscopy (UBM). We compared the differences in the parameters measured in both horizontal and vertical directions. The participants were categorized into three groups according to ciliary sulcus width (CSW) which is defined as the distance between the posterior angle of the iris and the anterior angle of the ciliary process: narrow CSW group (NSG); medium CSW group (MSG); and wide CSW group (WSG). The correlations between CLR/STSL and vault were examined in each of the three groups. Biased correlation analysis was used further to contrast the correlation between CLR/STSL and vault. RESULTS: This retrospective study included 223 myopic eyes. Vertical STSL (VSTSL) and vertical CLR (VCLR) exhibited significantly greater values compared to their horizontal counterparts (both P < 0.05). None of the indicators were statistically different between the three groups. In both NSG and MSG, STSL/CLR correlated with vault, while in WSG, only STSL correlated with vault (r=-0.316, P = 0.013). In contrast to HCLR, the correlation between HSTSL and vault remained after controlling for HCLR (r=-0.162, P = 0.015). CONCLUSIONS: STSL should deserve more attention in the preoperative evaluation of ICL compared to CLR especially when CSW is large.

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.

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.

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.

The effect of cumulative energy in repeated subliminal transscleral cyclophotocoagulation: a retrospective study.

BACKGROUND: The long-term safety and efficacy of repeated applications of subliminal transscleral cyclophotocoagulation (SL-TSCPC) with a focus on cumulative energy was evaluated in glaucoma patients. METHODS: In this retrospective, multicentric study the data of a total of 82 eyes with various causes of glaucoma that were treated with a single or multiple applications of SL-TSCPC were collected. Treatments were performed under general or local anesthesia with an 810 nm diode laser. Power was 2000 mW; duty cycle, 31.3%; total treatment duration, 80-320 s; equaling a total energy of 50-200 J per treatment session. Fifty-five eyes (55 patients) presented for all follow-ups, and these eyes were selected for further statistical analysis. The mean age was 60.0 ± 17.1 years, and 22 (40%) of the patients were female. Intraocular pressure (IOP) and dependence on further glaucoma medication were evaluated at 12 months following the initial treatment. RESULTS: Eyes underwent 1 or 2 consecutive SL-TSCPC treatments. Median (min-max) baseline IOP of 34 (13-69) decreased to 21.5 (7-61), 22 (8-68), 20 (9-68), and 19.5 (3-60) mmHg at the 1, 3, 6, and 12-month postoperative timepoints respectively. The mean (± SD) IOP decrease at 12 months was 26 ± 27%, 39 ± 32%, and 49 ± 33% in the low (below 120 J, n = 18), medium (120-200 J, n = 24), and high (above 200 J, n = 13) cumulative energy groups respectively. At the 12-month timepoint, oral carbonic anhydrase use was discontinued in ¾ of the cases. CONCLUSIONS: It was found that the repeated application of SL-TSCPC safely and efficiently decreases IOP in a Caucasian population with heterogenous causes of glaucoma, eyes with silicone oil responded to a greater extent. Inclusion of cumulative energy scales may contribute to better addressing repeated procedures in a standardized fashion.

Micropulse transscleral cyclophotocoagulation (MP-CPC): efficacy endpoints for the treatment of refractory paediatric glaucoma - a retrospective case-series.

BACKGROUND: This study evaluates the efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-CPC) in paediatric patients. METHODS: This retrospective case-series recruited 44 eyes for glaucoma patients who were younger than 17 years and were treated with MP-CPC and followed for at least one year. Pre- and post-intervention intraocular pressure (IOP) was compared out to at least one year postoperatively. Success rates at 6 months and 1 year postoperatively were assessed. P < 0.05 was considered statistically significant. RESULTS: There were 35 (79.5%) eyes with a history of glaucoma surgery. IOP decreased statistically significantly from a baseline of 32.7 (standard deviation:8.7 mmHg) to 23.2 (8.6) and 21.7 (7.9) mmHg at the 6 months and 1-year follow-up, respectively (P < 0.0001, all comparisons). Overall success was noted in 19 (47.5%) eyes at the 6 months follow-up, and 23 (53.5%) eyes at 1 year. CONCLUSIONS: MP-CPC reduces IOP and the burden of medications in paediatric patients with glaucoma. Additionally, its safety profile favours the use of MP-CPC as an adjunctive modality for refractory glaucoma.

Ciliary muscle and anterior segment characteristics in pre-presbyopic adults with Down syndrome.

PURPOSE: Previous research has shown that accommodation deficits are common in individuals with Down syndrome (DS), but the origin and mechanisms behind these deficits are still unknown. The aim of this study was to investigate the characteristics of different ocular structures involved in accommodation, in particular the ciliary muscle (CM), in a population of individuals with DS to further understand this deficit and its mechanisms. METHODS: Thirty-two volunteer participants of pre-presbyopic age with (n = 16) and without DS (n = 16) were recruited. Temporal and nasal images of the CM were acquired using anterior segment optical coherence tomography (AS-OCT) while participants fixated an eccentrically located target. Analysis of CM parameters was undertaken using validated semi-automated software. Axial length, anterior chamber depth, lens thickness and corneal curvature were obtained with the Topcon Aladdin Optical Biometer and Corneal Topographer. Non-cycloplegic refractive error and accommodative ability were obtained with an open-field autorefractor and dynamic retinoscopy, respectively. Independent t-tests were conducted to determine differences in CM and other anterior segment parameters between participants with and without DS. RESULTS: No significant differences were found in the CM parameters studied between participants with and without DS (p > 0.05). In contrast, significant differences were found in visual acuity (p < 0.001), accommodative response (p < 0.001) and corneal curvature (K1 p = 0.003 and K2 p < 0.001) between participants with and without DS. CONCLUSIONS: Despite having poorer accommodation, pre-presbyopic adults with DS do not have a different CM morphology to that found in typically developing adults. These findings suggest that the accommodative deficit found in this population is not due to a mechanical deficit of the CM.

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.