The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

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.

Pigmented medulloepithelioma of the optic nerve: A challenging diagnostic entity.

Because of its rarity, the diagnosis of optic nerve medulloepithelioma poses a real diagnostic challenge. Medulloepithelioma is a congenital tumor that derives from the primitive medullary epithelium present in the neural tube and the optic vesicle. Its classical location is the ciliary body. Cases of retinal or optic nerve locations have been rarely reported in the literature. Only 11 cases have been published in the English literature. Herein, we report the case of a 2-year-old boy who underwent enucleation of the right eye for a presumed diagnosis of right-eye retinoblastoma, based on the presence of leukocoria on ophthalmological examination. Pathological examination showed an optic nerve medulloepithelioma. A review of the literature is also discussed in our work.

Vitamin D and myopia: a review.

Myopia is a worldwide public health problem of vision disorder caused by multiple factors, which has posed a huge socioeconomic burden, raising concerns about sight-threatening ocular complications. Vitamin D, as a kind of fat-soluble vitamin, related to time-spent-outdoors, has been considered by extensive studies to have potential relationship with myopia. We reviewed studies published in a decade which estimated the association of blood vitamin D status with myopia and summarized the universality and individuality of all research articles. Several research articles suggested the known environmental risk factors of myopia, including age, gender, ethnicity, education level, parental and school conditions, time-spent-outdoors, and sunlight exposure, and recent epidemiological studies demonstrate that increased vitamin D levels, by virtue of the extended outdoor time, may be an important modifiable factor and a protective effect that delay the progression of myopia in children and adolescents rather than in adults. The genetic studies have been conducted to get access to the evidence of gene polymorphism for explaining the association of serum vitamin D status and myopia, but the precise genetic interpretation of vitamin D and myopia remains unclear so far; on the other hand, the possible mechanisms are various like copolymerization mechanism, calcium homeostasis and imbalance of ciliary muscle function regulation, but nearly all of the investigators are inclined to remain skeptical. This article reviews the age-related epidemiological proofs, existent genetics correlations, possible underlying biological mechanisms and further values for the protective association between vitamin D and myopia, providing the possibility of prevention or postponement for myopia.

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.

Neurotrophic Keratopathy in Marfan Syndrome Patient After Micropulse Transscleral Cyclophotocoagulation: A Call for Risk Stratification.

BACKGROUND Micropulse transscleral cyclophotocoagulation is a non-invasive, widely employed procedure that uses diode laser to target the ciliary body to lower the intraocular pressure. Despite its acknowledged efficacy, certain complications are recognized, with neurotrophic keratopathy being a rare yet serious consequence. This report seeks to shed light on a potential high-risk subgroup susceptible to neurotrophic keratopathy, exemplified by our patient with Marfan syndrome, a condition characterized by thin sclera. CASE REPORT Our patient, who was confirmed to have Marfan syndrome with pseudophakic glaucoma, underwent micropulse transscleral cyclophotocoagulation due to high intraocular pressure bilaterally and subsequently quickly manifested neurotrophic keratopathy in both eyes postoperatively. Swift initiation of management involved a comprehensive approach, including topical antibiotics, preservative-free lubrication, medroxyprogesterone acetate 1%, serum balanced salt solution (BSS) 50%, and the application of bandage contact lenses to expedite healing. Fortunately, the left eye demonstrated resolution within 10 days, while the right eye exhibited delayed healing, leading to subsequent scarring. CONCLUSIONS This report highlights the critical importance of recognizing populations predisposed to neurotrophic keratopathy before subjecting them to micropulse transscleral cyclophotocoagulation. Such awareness allows for the fine-tuning of procedural parameters, offering a strategic approach to mitigate the risk of neurotrophic keratopathy development. By further exploring and recognizing potential risk factors, clinicians can enhance patient outcomes and refine the safety profile of micropulse transscleral cyclophotocoagulation.

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.

Cytomegalovirus detected by qPCR in iris and ciliary body of immunocompetent corneal donors.

BACKGROUND: Cytomegalovirus (CMV) can cause a wide panel of ocular infections. The involvement of CMV as a cause of anterior uveitis in the immunocompetent patient is recent and remains poorly understood. OBJECTIVE: To investigate the presence of CMV in anterior uveal tissues of immunocompetent corneal donors. STUDY DESIGN: We collected aqueous humor, iris, and ciliary body from both eyes of 25 donors died at the Limoges University Hospital between January 2020 and July 2021. CMV serology was determined for all patients from post-mortem blood sample. Ocular tissues were split in 2 fragments for qPCR and 2 for histological analysis. CMV genomes copies were quantified by Multiplex qPCR after DNA extraction. RESULTS: 16 of 25 patients (64%) displayed positive CMV serology, with a median age of 67 years. Viremia was positive in 3 of 16 (19%) CMV-positive patients. No CMV DNA copies were found from the aqueous humor samples. CMV DNA was detected in iris and ciliary body of 28 of 32 eyes of seropositive donors, and 5 of 18 eyes of seronegative donors. The median viral copy number [IQR] was 2.41 × 102 [8.91 × 101 - 1.01 × 103] copies/1 × 106 cells in the CMV-positive group and 0.00 [0.00 - 3.54 × 102] copies/1 × 106 cells in the CMV-negative group (p<0.001). Histology and immunohistochemistry did not reveal any CMV lesions from any sample. CONCLUSION: CMV DNA was found in iris and ciliary body of immunocompetent seropositive patients, but also, although less frequently, from seronegative donors. These results highlight mechanisms of infection, latency and reactivation of CMV in ocular tissues.

Bruch's membrane and Brücke's muscle in the pars plana region.

PURPOSE: To examine Bruch's membrane (BM) in association with the longitudinal part of the ciliary muscle (LPCM) in the pars plana region. METHODS: Using light microscopy, we histomorphometrically assessed BM and the LPCM in the pars plana region. RESULTS: The histomorphometric study included 51 eyes (51 patients; mean age: 60.8 ± 15.0 years; axial length: 26.0 ± 3.3 mm; range: 21.0-36.0 mm). The LPCM (total length: 4.60 ± 1.10 mm) ended 1.15 ± 0.56 mm anterior to the ora serrata. Within the pars plana region, the LPCM (length: 2.58 ± 0.98 mm) had direct contact with BM for 1.95 ± 0.99 mm (71.1 ± 18.4% of the BM undersurface), while a capillary layer was interposed between the BM and the LPCM for 0.70 ± 0.40 mm (29.0 ± 18.4%). In the pars plana region free of LPCM close to the ora serrata, the percentage of BM covered by the capillary layer was higher than in the pars plana region containing the LPCM (63.0 ± 42.1% vs. 29.0 ± 18.4%; p < 0.001). At the LPCM end, BM was in direct contact with a collagenous tissue from the LPCM and was focally thickened as compared to BM with an underlying capillary layer (9.5 ± 5.3 µm vs. 4.3 ± 1.2 µm; p < 0.001). CONCLUSIONS: The direct contact of BM with the LPCM in the pars plana in association with focal BM thickening at the LPCM end suggests an insertion of LPCM on the BM. Taking into account the biomechanical strength of BM, it may imply a functional unit of the LPCM with BM in the process of accommodation with a secondary movement of the posterior BM and tertiary thickening of the subfoveal choroidal space.

Modified technique for reconstruction of large cyclodialysis cleft with capsular tension ring and continuous and cerclage sutures without scleral flaps.

To present a modified technique for the reconstruction of a large cyclodialysis cleft with capsular tension ring (CTR) and continuous and cerclage sutures without scleral flaps in 12 cases. The mean visual acuity was 0.75 ± 0.47 logarithm of the minimal angle of resolution (logMAR), and the average intraocular pressure (IOP) was 3.35 ± 0.41 mmHg before surgery. Ultrasound biomicroscopy (UBM) revealed a ciliary cleft of 4.3 ± 3.5 clock hours. We performed the modified technique for the reconstruction of a large cyclodialysis cleft. Postoperative visual acuity improved to 0.48 ± 0.26 logMAR, and the IOP improved to 15.88 ± 3.81 mmHg. Postoperative UBM showed that cyclodialysis disappeared in the whole circumference of 12 eyes. The postoperative complications included 42% (5 eyes) with a temporary elevation of IOP and 16% (2 eyes) with a posterior shift of the ciliary body. No other complications were detected during the follow-up. Based on the results, our modified technique might be useful for most cyclodialysis clefts.

Micropulse cyclophotocoagulation compared to continuous wave cyclophotocoagulation for the management of refractory pediatric glaucoma.

INTRODUCTION: Micropulse cyclophotocoagulation (MPCPC) has been shown in adults to offer a favorable post-operative safety profile compared to continuous wave transscleral cyclophotocoagulation (CWCPC) in the management of glaucoma. The purpose of this study is to evaluate the long term efficacy, safety, and effectiveness of MPCPC in the management of pediatric glaucoma when compared to CWCPC. METHODS: IRB approved retrospective chart review of patients with pediatric glaucoma that underwent MPCPC and CWCPC at 2 separate institutions. Success was defined as intraocular pressure (IOP) between 5 and 21mmHg on any number of topical glaucoma medication without requiring additional surgical intervention or oral IOP lowering medication. RESULTS: Of the 48 patients in the study, 22 (26 eyes) underwent MPCPC and 26 (30 eyes) underwent CWCPC. At 1 year, 7 out of 26 eyes (26.9%) achieved success in the MPCPC group compared to 13 out of 30 eyes (43.3%) in the CWCPC group. Survival analysis unveiled a statistically significant difference in success between the two groups (p = 0.03). CONCLUSION: In pediatric glaucoma patients undergoing cyclophotocoagulation procedures, CWCPC outperformed MPCPC using default settings in terms of achieving long-term IOP control. Additional studies are required to evaluated augmented MPCPC settings in pediatric glaucoma patients.

Long-term outcomes of cyclophotocoagulation in refractory pediatric glaucoma: treatment response and success in 262 eyes.

PURPOSE: To report the surgical success and response to treatment for children undergoing cyclophotocoagulation (CPC) for refractory pediatric glaucoma. METHODS: The medical records of children with a diagnosis of glaucoma who underwent a first CPC between May 2000 and May 2020 were reviewed retrospectively. The cumulative probability of success was assessed. For definition 1, treatment success was defined as IOP ≤21 mm Hg at all the visits after the first 3 months without the need for additional glaucoma surgery or repeat CPC. For definition 2, repeat CPC did not constitute failure. RESULTS: Of 300 eyes that underwent CPC, we identified 262 eyes eligible for inclusion. The mean age at time of first treatment was 5.33 ± 5.03 years, with a mean follow-up of 4.3 ± 4.2 years (31 eyes having at least 10 years of follow-up). The success rates for definitions 1 and 2 were 26.7% (95% CI, 21.7%-32.4%) and 46.2% (95% CI, 40.2%-52.3%), respectively. Older age was associated with a lower risk of failure after both single CPC (HR, 0.92; 95% CI, 0.88-0.96; P < 0.001) and multiple CPCs (HR, 0.95; 95% CI, 0.90-1.00, P = 0.073). Of the 262 eyes, 107 (41%) had sustained IOP-lowering with a single treatment and 56 (21%) with multiple treatments; 35 (13%) had a transient response, and 64 (24%) had no response. CONCLUSIONS: Glaucoma control through CPC often requires multiple treatments, with around a quarter of children responding suboptimally. Older children are more likely to exhibit successful IOP lowering.

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.

Comparison of Efficacy of Micropulse and Continuous Wave Cyclophotocoagulation in Patients With Pediatric Glaucoma.

PRCIS: Both micropulse (MP-CPC) and continuous wave (CW-CPC) cyclophotocoagulation exhibited short-term effectiveness in lowering IOP, followed by reversion to near baseline levels 12 months after laser treatment. OBJECTIVE: To determine and compare the effectiveness and safety of MP-CPC and CW-CPC in patients diagnosed with pediatric glaucoma. METHODS: A retrospective cohort study was conducted on a total of 28 patients (81 eyes) diagnosed with pediatric glaucoma either undergoing MP-CPC or CW-CPC. Intraocular pressure (IOP) measurements, number of glaucoma medications, and the onset of complications were collected at baseline, 1-month, 3-month, 6-month, and 12-month intervals. Success rate (SR) was defined as eyes achieving IOP ≤21 mm Hg and ≥5 mm Hg and a 20% reduction in IOP at the last follow-up visit. RESULTS: All patients either undergoing MP-CPC or CW-CPC were matched for age (mean ± SD; 1.76 ± 1.69 vs 1.56 ± 2.49 y). Patients undergoing MP-CPC had significant decreases in IOP from baseline IOP at 1, 3, and 6 months with a 22% SR at 12 months. CW-CPC had a significant decrease in IOP from baseline IOP at all follow-ups, with a 27% SR at 12 months. At the 12-month follow-up, the CW-CPC cohort exhibited a significantly larger overall drop in IOP when compared with the MP-CPC cohort, (7.99 ± 7.95 vs 1.78 ± 6.89, P < 0.05); however, the difference in SR between treatment groups (27% vs 22%) at 12 months was not significant ( P > 0.05). Complications were minimal for both groups. CONCLUSION: Both MP-CPC and CW-CPC exhibited short-term effectiveness in lowering IOP, followed by reversion to near baseline levels 12 months after laser treatment. Both MP-CPC and CW-CPC exhibited similar SR at 12 months, 22% and 27% respectively.

Diode Laser Transscleral Cyclophotocoagulation With a Novel Low-Cost Torchlight Method of Trans-Corneal Transillumination in Refractory Pediatric Glaucoma.

PRCIS: Trans-corneal transillumination (TI) aided transscleral cyclophotocoagulation (TSCPC) for intraocular pressure control of refractory pediatric glaucoma was found to be effective at 1 year. PURPOSE: To study 1-year outcomes of diode laser TSCPC with trans-corneal TI using a novel low-cost torchlight method in refractory pediatric glaucoma. METHODS: This prospective interventional study included children with refractory glaucoma who underwent TSCPC with the Oculight laser system (IRIS Medical Instruments) with trans-corneal TI (TSCPC-TI) using a novel low-cost torchlight method. Children completing a minimum 1-year follow-up were analyzed. They were compared with a historical control group of children who underwent TSCPC without TI (TSCPC-No-TI) at the 1-year follow-up period. We analyzed the mean laser energy delivered, post-laser intraocular pressure reduction, number of antiglaucoma medications (AGM), the requirement of retreatment and complications of the procedure in both groups. RESULTS: Forty-two eyes of 35 patients comprised the TSCPC-TI group and were compared with 31 eyes of 21 patients in the TSCPC-No-TI group. The TSCPC-TI group required lower energy than the TSCPC-No-TI group (24.7±7.8 J vs. 47.2±10.9 J, P <0.0001). Mean topical antiglaucoma drug requirement decreased from 2.9±0.08 before treatment to 0.66±0.8 at the end of 1 year in TSCPC-TI and from 2.6±1.0 before treatment to 0.6±0.77 in the TSCPC-No-TI groups, respectively ( P =0.15). There was a significantly reduced dependence of oral acetazolamide in the TSCPC-TI group at 1-year follow-up [5.7% vs. 61.9%, respectively ( P <0.001%)]. No adverse event of hypotony or choroidal detachment was noted in any group. CONCLUSIONS: TSCPC aided by TI with a low-cost torchlight for pediatric refractory glaucoma was found to be effective at 1 year in reducing intraocular pressure and the burden of medication.

Efficacy and safety of transscleral cyclophotocoagulation versus cyclocryotherapy in the treatment of intractable glaucoma: A systematic review and meta-analysis.

To perform a meta-analysis to compare the efficacy and safety of diode laser transscleral cyclophotocoagulation (TSCPC) and cyclocryotherapy (CCT) in the treatment of intractable glaucoma. Systemic searches of the Ovid MEDLINE, EMBASE, and Cochrane Library databases yielded experimental and observational comparative studies. TSCPC and CCT efficacy and safety outcomes were compared. Subgroup analyses of participant ethnicity, preoperative intraocular pressure (IOP) level, and underlying causes of glaucoma were conducted. The pooled effects were computed using the random-effects model. The meta-analysis included nine studies totalling 668 eyes. There was no statistically significant difference between the TSCPC and CCT groups in the IOP reduction (IOPR%), decrease in antiglaucoma medications, the operative success rate with or without medications, or retreatment rate in the efficacy analysis. In the subgroup analysis, CCT had a better IOP-lowering effect among non-Asian participants and a non-inferior IOPR% to TSCPC among Asian participants. TSCPC and CCT were associated with similar rates of deterioration in visual acuity, postoperative visual analog scale, and other analysed postoperative complications in the safety analysis. In both groups, severe complications were uncommon. Diode laser TSCPC and CCT had nearly equivalent clinical efficacy in treating intractable glaucoma, while CCT demonstrated a better IOP-lowering effect in non-Asian. Both cyclodestructive procedures have a comparable safety profile.