CaMKII-based gene therapy protects retinal ganglion cells in a broad range of disease: ischemic retinopathy and congenital glaucoma.

Reduced Accommodation Without Mydriasis After Micropulse Cyclophotocoagulation in a Young Congenital Glaucoma Patient: A Case Report

We report the clinical history of two siblings, initially diagnosed with juvenile glaucoma (JG), who were subsequently found to harbor a novel pathogenic OPA1 splicing variant consistent with dominant optic atrophy (DOA). The male proband presented with elevated intraocular pressure (IOP) at age 11, while his sister had normal IOP values at age 16. Both developed bilateral temporal optic nerve pallor, central visual field defects, and reduced color vision. Optical coherence tomography (OCT) confirmed thinning of the retinal nerve fiber and ganglion cell layers. Whole exome sequencing identified a novel splice-site variant in OPA1 (NM_130837.3:c.611-2A>T) in both siblings and their affected mother, classified as pathogenic according to ACMG/AMP guidelines. During treatment washout, the male proband showed elevated IOP, consistent with concomitant JG and DOA, whereas the sister exhibited DOA only. This report highlights the importance of considering DOA in young patients with presumed JG, and suggests potential overlapping pathophysiology involving mitochondrial dysfunction and retinal ganglion cells vulnerability.

A 7-year-old boy, diagnosed with bilateral congenital glaucoma presented with elevated intraocular pressure (IOP). Anterior segment optical coherence tomography (AS-OCT) of the right eye revealed an artificial plane within the Haab's striae (HS), corresponding to separation of the Descemet membrane-pre-Descemet layer (DM-PDL) complex. Following medical reduction of IOP, slit-lamp examination demonstrated linear reddish discoloration within the HS, which was confirmed on AS-OCT as a hyperreflective intra-lamellar collection of blood between the posterior stroma and endothelium. The eye had not undergone any previous intraocular surgery or trauma. This observation represents a unique instance of de novo intra-lamellar hemorrhage within Haab's striae in an unoperated eye. The presumed mechanism involves reflux of blood into Schlemm's canal, with secondary ingress into the artificial plane created by partial DM-PDL separation, possibly triggered by a Valsalva maneuvre combined with low IOP. This finding underscores the potential anatomical continuity between the PDL and the trabecular meshwork, as previously demonstrated histologically. Recognition of this phenomenon is important to distinguish it from postoperative endothelial hemorrhage or corneal blood staining and to expand our understanding of corneal structural responses in congenital glaucoma. To our knowledge, this is the first reported case demonstrating intra-lamellar bleeding within a pre-existing Haab's striae, documented non-invasively using high-resolution AS-OCT.

We reported the clinical course of refractory childhood glaucoma associated with Sturge–Weber syndrome (SWS) treated with Baerveldt glaucoma implant (BGI). The patient was a 14‐year‐old male diagnosed with SWS after birth. He had previously undergone four trabeculotomies for glaucoma and vitrectomy for submacular hemorrhage from a diffuse choroidal hemangioma in his left eye. Before the BGI surgery, his intraocular pressure was 30 mmHg under full medications. The patient experienced extensive serous retinal and choroidal detachments on Postoperative Day 9. The cause may have been the increased leakage of serous fluid from the choroidal hemangioma and the high venous pressure in the episclera due to SWS. Retinal and choroidal detachments subsided within 8 days with conservative therapy. It is important to avoid postoperative hypotony for the treatment of secondary childhood glaucoma due to SWS.

Using Genetics for Glaucoma Screening and Risk Stratification: The LXXXII Edward Jackson Memorial Lecture.

Background: The CYP1B1 gene is typically associated with congenital glaucoma and certain cancers, but its role in metabolic regulation remains less understood. We report a case that suggests a possible new connection between CYP1B1 mutations and pancreatic islet cell hyperplasia. Case Presentation: Our patient, a 12-year-old boy with a known history of congenital glaucoma and familial Mediterranean fever (FMF), presented with recurrent hypoglycemic episodes initially thought to be seizures due to epilepsy. Further workup revealed high insulin levels during these episodes. A PET/CT scan eventually identified a lesion in the pancreas, and surgery confirmed islet cell hyperplasia. Following resection, his hypoglycemic episodes resolved. Genetic testing revealed a homozygous mutation in CYP1B1, along with a known MEFV variant linked to FMF. Discussion: This appears to be the first reported case linking a CYP1B1 mutation to islet cell hyperplasia. One theory is that the gene’s role in hormone and lipid metabolism, as well as oxidative stress regulation, may influence β-cell activity. Chronic inflammation from FMF could have also contributed to pancreatic stress or compensatory hyperplasia. Conclusion: This unusual case raises important questions about the metabolic roles of CYP1B1. It also highlights the value of genetic testing in unexplained cases of hyperinsulinemic hypoglycemia, especially in patients with complex medical histories.

To investigate the vision improvement of corneal rigid gas permeable contact lenses (RGPCLs) in children with primary congenital glaucoma (PCG), compared with spectacles. This cross-sectional analysis used baseline data from a randomized trial (CLEVR-PCG Study) investigating RGPCLs' impact on postoperative vision rehabilitation in children with PCG with controlled intraocular pressure from April 2022 to August 2023. The study included 51 eyes from 29 children aged 7.41±2.51 years. Refractive errors were corrected first with spectacles, then RGPCLs. Best spectacle-corrected visual acuity (BSCVA) and best RGPCL-corrected visual acuity (BCLVA) and contrast sensitivity function (CSF) were compared. BCLVA was better than BSCVA, and CSF with RGPCLs was better than with spectacles: BCLVA 0.30 (0.15, 0.52) LogMAR vs. BSCVA 0.40 (0.30, 0.70) LogMAR; area under the logarithm of the CSF (AULCSF) 0.68±0.38 vs. 0.51±0.33; CSF acuity 0.94±0.29 vs. 0.83±0.29 (all P<0.001). Multivariate linear regression showed greater myopic spherical equivalent (SER) associated with greater BCVA improvement (β=0.01, 95% CI: 0.004-0.02; P<0.001) and CSF acuity improvement (β=-0.01, 95% CI: -0.01 to -0.0005; P=0.036). Greater myopic SER (β=-0.01, 95% CI -0.02 to -0.004) and better BSCVA (β=-0.18, 95% CI: -0.32 to -0.04) associated with greater AULCSF improvement (P=0.007). RGPCLs immediately improved vision in children with PCG. These findings suggest that RGPCLs are potentially useful for visual rehabilitation in this population.

EndoArt is a novel endothelial keratoprosthesis recently introduced to treat corneal endothelial decompensation. Retroprosthetic membrane (RPM) formation after EndoArt implantation has not been described. This article reports its incidence, risk factors, and management, along with histological analysis. A retrospective analysis of patients who underwent EndoArt implantation at Cologne University Hospital (Germany) between June 2023 and March 2025 was conducted. Eyes with RPMs were identified using routine anterior segment optical coherence tomography. Clinical data, treatment approaches, and surgical outcomes were analyzed. Surgical membranectomy was performed in one eye and analyzed by light microscopy with hematoxylin-eosin staining and immunohistochemistry. Sixty-nine eyes underwent EndoArt implantation, and 3 (4.35%) developed RPMs. The main indication was endothelial failure with chronic corneal edema in eyes at high risk of graft failure. Risk factors included multiple previous failed Descemet membrane endothelial keratoplasty (n = 3), aphakia (n = 2), glaucoma (n = 2; one with congenital glaucoma, one with angle-closure glaucoma), glaucoma surgery (n = 1), aniridia (n = 1), iridocorneal endothelial syndrome (n = 1), cyclodialysis (n = 1), artificial iris (n = 1), and pseudophakia (n = 2). The mean time to RPM formation was 7.3 months. One eye had a recurrence 2 months after membranectomy. Histology revealed abundant type III collagen (vimentin+) and macrophages (CD68+), but no significant leukocytes (CD45-) or myofibroblasts (α-SMA-), suggesting chronic remodeling without acute inflammation. RPM formation after EndoArt implantation is rare and has not been previously described. Surgical removal improves clinical outcomes and preserves implant stability; however, recurrence may occur, highlighting the need for follow-up and additional research. RPM formation may result from chronic blood-aqueous barrier breakdown in eyes with altered anatomy and a history of multiple surgeries.

The purpose of this study is to assess the 24-month outcomes of trabeculotomy in paediatric patients with steroid-induced ocular hypertension or glaucoma who did not achieve adequate intraocular pressure (IOP) control under maximal medical therapy. A retrospective case series was conducted at Copenhagen University Hospital-Rigshospitalet between February 2018 and January 2022. 13 eyes of eight consecutive paediatric patients (aged 7-17 years) undergoing trabeculotomy for steroid-induced ocular hypertension or glaucoma were included. IOP, the number of pressure-lowering medications (PLMs) used, steroid exposure, visual acuity and postoperative complications were documented over a 24-month follow-up. Complete success was defined as achieving IOP of ≤21 mm Hg without the need for PLMs. Mean preoperative IOP was 29.7 mm Hg despite intensive use of PLMs. Postoperatively, mean IOP decreased significantly, remaining below 16 mm Hg at all postoperative follow-ups with a mean IOP of 15.1 mm Hg at 24 months. All eyes were off PLMs postoperatively, and complete success was achieved in all eyes through 24 months with no postoperative complications. Visual acuity showed slight improvement, though this was not statistically significant. Despite continued corticosteroid use for underlying conditions, no IOP elevation recurred. Trabeculotomy is a safe and effective surgical option for paediatric steroid-induced ocular hypertension or glaucoma, ensuring long-term IOP control without the need for further medication or surgical intervention. This procedure should be considered early in paediatric steroid responders when medical therapy fails to manage IOP adequately, minimising the risk of steroid-induced glaucoma.

Pediatric glaucoma following surgery (GFS) remains a serious postoperative complication with potential for vision loss. Although glaucoma drainage devices are widely used in this setting, high-quality pooled evidence on the Baerveldt glaucoma implant (BGI) in children is limited. To systematically evaluate the efficacy and safety of BGI in pediatric patients with GFS. Following PRISMA guidelines, five databases were searched up to August 2025. Eligible studies included pediatric cohorts (≤ 18years) undergoing BGI after surgery, reporting intraocular pressure (IOP) outcomes or surgical success. Data were pooled using random-effects meta-analysis. Five studies (116 patients) met inclusion criteria. The mean age ranged from 3.0-7.8years, with average follow-up of 31months. The pooled success rate of IOP control was 84.5% (95% CI 0.75-0.91), with no evidence of heterogeneity. Hypotony occurred in 7.5%, choroidal effusion in 9%, and rare events included phthisis bulbi (2%), endophthalmitis (1.4%), and corneal decompensation (3.3%). BGI provides effective and relatively safe IOP control after surgery, with complication rates comparable to or lower than alternative surgical options. However, the current evidence is limited by small sample sizes, retrospective study designs, and short- to mid-term follow-up. Long-term, multicenter prospective studies are needed to better define its long-term safety and efficacy.

BackgroundTo assess the agreement between intraocular pressure (IOP) measurements obtained with the iCare IC200 rebound tonometer during natural sleep and under general anesthesia (EUA) in children under 3 years of age with glaucoma, and to evaluate the impact of this approach on clinical follow-up frequency and anesthesia exposure.MethodsThis prospective study included 74 eye-session pairs from 74 eyes of 27 patients aged 0–36 months diagnosed with pediatric glaucoma. IOP was measured during natural sleep within ≤ 2 h prior to EUA under end-tidal sevoflurane 2–3%. Measurements were performed by the same examiner under both conditions. Office and EUA frequencies were compared to a historical cohort (2009–2012) to evaluate changes in clinical monitoring trends.ResultsMean age was 18.07 ± 13.97 months; 78% had primary congenital glaucoma. Natural sleep IOP (21.01 ± 11.77 mmHg) was consistently higher than EUA IOP (17.69 ± 9.85 mmHg), with mean difference of 3.32 ± 3.83 mmHg (14.96 ± 16.60%) (p < 0.05). A very strong correlation was observed between the two measurement conditions (r = 0.95, R² = 0.91). Current surveillance demonstrated 4.45 ± 2.70 EUA procedures versus 3.18 ± 2.44 office visits per patient, compared to pre-iCare era ratio of 7.39 ± 2.65 EUA versus 0.80 ± 0.70 office visits, representing a 40% reduction in anesthesia dependence.ConclusionNatural-sleep rebound tonometry supports bias-aware, clinic-based trend monitoring and can reduce anesthesia exposure in children under 3 years.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12886-025-04549-z.

To evaluate the effects of topical prostaglandin E2 receptor 2 (EP2) agonist, omidenepag isopropyl (OMDI), on intraocular pressure (IOP) and pupil diameter (PD) in normal cats and cats with feline congenital glaucoma (FCG). Ten FCG cats and 8 normal cats. In this prospective, randomized, placebo-controlled, masked pilot study, normal and FCG cats received one drop of 0.002% OMDI ophthalmic solution in one eye and artificial tears in the contralateral eye. IOP and PD were measured by a masked observer at baseline and at multiple time points up to 32-36 h post-administration. Topical 0.002% OMDI significantly lowered IOP compared to controls in both normal and FCG cats. In normal cats, the effect was significant up to 12 h after instillation, with a maximal reduction from baseline of 7.3 mmHg (43.5%). In FCG cats, the effect was significant from 2 to 8 h after instillation, with a maximal reduction from baseline of 16.7 mmHg (60.2%). No significant effect on pupil diameter or signs of ocular irritation was observed in either group. A single topical drop of 0.002% OMDI significantly lowers IOP in normal and FCG cats without inducing miosis. Our findings support that topical selective EP2 agonists may be a promising therapeutic option for feline glaucoma and provide information relevant to dosing intervals for future studies.

To report and present imaging of a case of reversal of optic disc cupping following filtering surgery in juvenile glaucoma. A 22-year-old woman visited our emergency department complaining of blurred vision in her right eye for two weeks associated with bilateral ocular pain. Her medical history included bilateral juvenile glaucoma treated since 2018, occurring in the context of a significant family history of glaucoma. On initial examination, intraocular pressure was 43mmHg in both eyes. Fundus examination showed bilateral optic disc cupping. Humphrey perimetry revealed advanced glaucomatous scotomas surrounding fixation. Filtering surgeries were performed: a deep non-perforating sclerectomy for the right eye followed by a trabeculectomy for the left. Transient hypotony retinopathy occurred in both eyes. Intraocular pressure reduction was followed by a reversal of the optic disc cupping. This morphologic recovery was not associated with improvement in other structural parameters such as retinal nerve fiber layer or ganglion cell complex thickness or perimetric functional indices. This is a rare case of reversal of optic disc cupping in an adult. This case highlights the dynamic sclerolaminar movements involved in the pathogenesis of glaucoma and raises the question of the consequences of these kinetics.

Virtual reality field testing in children with normal eyes and glaucoma: comparison of game-based versus Humphrey visual field-equivalent algorithms.

Short stature in children with primary congenital glaucoma-a retrospective cross-sectional study.

Conventional glaucoma drainage devices (GDDs), such as the Ahmed Glaucoma Valve and Baerveldt Glaucoma Implant, are widely used in childhood glaucoma. Recently, newer surgical options, including the PRESERFLO microshunt, Paul Glaucoma Implant (PGI), eyePlate-S, and ClearPath, have emerged with potential advantages to childhood glaucoma patients. This review summarizes current evidence regarding the design, outcomes, and safety profiles of these newer implants in childhood glaucoma patients. The PRESERFLO offers a minimally invasive approach with favorable safety and intraocular pressure (IOP)-lowering outcomes in small pediatric case series, including eyes with prior GDD implantation. It is typically used with adjunctive mitomycin C. Technical modifications, such as ripcord insertion, reduce the risk of postoperative hypotony.The PGI features a valveless design that enables controlled flow via a 6-0 Prolene ripcord without external ligation. Additionally, its design reduces contact with the corneal endothelium and extraocular muscles. Retrospective series and early randomized data suggest good IOP control with an acceptable safety profile. The eyePlate-S features a valveless design that allows controlled flow through a 5-0 Prolene ripcord, eliminating the need for external ligation. Its tube has an external diameter comparable to the PGI (0.47 mm) but a larger internal diameter (0.18 mm in the eyePlate-S vs. 0.13 mm in the PGI). The eyePlate-200S can also be positioned between extraocular muscles, which may reduce the risk of postoperative diplopia. In addition, the thin, flexible silicone plate can be folded to facilitate implantation.The ClearPath enables flexible implantation in complex pediatric anatomy. Early multiyear results show sustained IOP reduction and decreased medication burden, with a success rate of 79% at 4 years. Newer devices such as the PRESERFLO, PGI, and ACP demonstrate encouraging mid-term efficacy and safety in the management of childhood glaucoma, particularly in refractory cases or eyes with prior surgeries. While early outcomes are promising, larger comparative studies with extended follow-up are needed to better establish their long-term role relative to conventional GDDs in childhood glaucoma management.

Congenital nasolacrimal duct obstruction (CNLDO) represents the most prevalent cause of epiphora in infancy, with a reported incidence of approximately 6-20% of newborns. In the majority of cases, a membranous occlusion at the valve of Hasner is responsible, with spontaneous resolution occurring in up to 96% within the first year of life.Clinical signs comprise persistent tearing, an elevated tear meniscus and recurrent mucopurulent discharge; digital pressure on the lacrimal sac may induce retrograde reflux. Ophthalmic examination is indispensable to exclude differential diagnoses such as congenital glaucoma, keratoconjunctivitis or eyelid malposition.Given the high probability of spontaneous resolution, conservative management is the treatment of choice during the first 6-12 months of life, including parental instructions, consistent lid hygiene, and lacrimal sac massage. Topical antibiotics should be restricted to short-term application in the presence of bacterial superinfection.In cases of persistent obstruction or complicated disease lacrimal probing is indicated, usually after 12 months of age in general anaesthesia. Silicone intubation is recommended for complex or recurrent obstructions, failed probing, or in older children, and associated with substantially improved success rates. Endoscopic techniques including transcanalicular dacryoendoscopy, ballon dacryoplasty, and endonasal endoscopy can be helpful in refractory and anatomically complex cases. Dacryocystorhinostomy serves as ultima ratio surgery in treatment-refractory or bony stenosis and should not be performed before the age of one year.A staged, evidence-based therapeutic management beginning with conservative measures and escalating to age- and anatomy-adapted interventions, is recommended to achieve favourable outcomes.

Primary congenital glaucoma (PCG) surgery often leaves residual visual impairment in children. Evidence comparing rigid gas-permeable contact lenses (RGPCLs) vs spectacles for rehabilitation is needed. To compare the use of RGPCLs vs continued spectacle wear for improving visual outcomes for children after PCG surgery. This randomized clinical trial was conducted at Zhongshan Ophthalmic Center, a tertiary referral center in Guangzhou, China, from April 21, 2022, to August 21, 2023. Participants comprised 56 children (aged 4-15 years) with surgically managed PCG and poor spectacle response. Data were analyzed from October 11, 2023, to March 21, 2024. RGPCLs (n = 29) vs spectacles (n = 27) for 12 months, plus standardized amblyopia patching. The primary outcome was change in worse-eye best-corrected visual acuity (BCVA) at 12 months measured by the Early Treatment Diabetic Retinopathy Study chart with tumbling-E optotypes with children wearing their current best refractive correction. Secondary outcomes included contrast sensitivity function and near stereoacuity. Among 56 (of a total of 83 screened participants) randomized participants, 48 (85.7%) completed at least 1 follow-up visit and were included in the primary analysis. Baseline demographic and ocular characteristics for the RGPCL group vs the spectacles group included a mean (SD) age of 7.7 (2.7) vs 7.2 (3.2) years, 13 (54.2%) vs 14 (58.3%) male, and 11 (45.8%) vs 10 (41.7%) female. At 12 months, 22 of 29 participants (76.0%) in the RGPCL group and 19 of 27 participants (70.4%) in the spectacles group completed the final visit. The mean (SD) baseline worse-eye spherical equivalent was -6.55 (6.43) vs -5.17 (5.27) diopters, the mean (SD) BCVA was 0.99 (0.71) vs 1.02 (0.74) logMAR (approximate Snellen equivalent 20/200), and the mean (SD) intraocular pressure was 14.98 (3.14) vs 13.36 (3.92) mm Hg in the RGPCL vs the spectacles group, respectively. At 1 year, the RGPCL group had greater BCVA improvement (mean [SD], 0.31 [0.28] vs 0.12 [0.33] logMAR; adjusted treatment difference, -0.19 logMAR; 95% CI, -0.36 to -0.02 logMAR [approximately 10 letters]; P = .03). Achievement of 2 or more lines of BCVA improvement occurred in 15 of 24 participants (62.5%) in the RGPCL group vs 9 of 24 participants (37.5%) in the spectacles group (odds ratio, 6.83; 95% CI, 1.81-25.73; P = .01). The RGPCL group had greater contrast sensitivity function improvement (0.40 [0.27] vs 0.13 [0.32]; adjusted treatment difference, 0.24 log units; 95% CI, -0.01 to 0.49; P = .04). Near stereoacuity of 60 arcseconds or less was achieved by 12 participants (50.0%) vs 6 of 24 participants (25.0%) (odds ratio, 6.96; 95% CI, 2.41-6.51; P = .001). No serious adverse events occurred. These findings suggest that RGPCLs provided superior visual acuity and contrast sensitivity improvement vs continued spectacle wear for children after PCG surgery. These findings support using RGPCLs for children undergoing PCG surgery, including those with worse baseline visual acuity or poor spectacle response. Chinese Clinical Trial Registry Identifier: ChiCTR2100043776.

This study identifies visual acuity and intraocular pressure at 3-year and 5-year follow-ups, along with other variables such as media opacity and nystagmus, as key predictors of long-term outcomes in childhood glaucoma, aiding better management and prognostication. This study aims to identify key predictive variables of visual acuity (VA) and intraocular pressure (IOP) outcomes in childhood glaucoma. By understanding these factors, the study seeks to improve prognostication and management strategies for pediatric patients. A retrospective analysis was conducted on pediatric glaucoma patients across multiple centers within the Childhood Glaucoma Research Network (CGRN). The study included patients with at least 5 years of follow-up. Variables such as sex, race, ethnicity, age of onset, laterality, and clinical measures including VA and IOP at various stages (initial visit, 3y, 5y, and final visits) were evaluated. Additional factors considered were anisometropia, media opacities, nystagmus, anterior segment dysgenesis (ASD), strabismus, and angle closure. The study included 396 eyes from 243 patients, with a mean age at presentation of 1.5 months. Several variables showed statistically and clinically significant correlations with final outcomes including IOP and VA at both 3-year and 5-year visits, as well as the presence of media opacities, unilateral glaucoma, nystagmus, and ASD. On the basis of multivariable prediction model analysis the 2 statistically significant predictors for visual acuity (n=31) were VA at 5-year visit and presence of angle closure. As for IOP outcomes (n=31), significant predictors included were IOP at 5-year visit and presence of nystagmus. This multicenter study highlights that VA and IOP measurements at 3 and 5 years postdiagnosis, along with the presence of specific ocular conditions such as media opacity and nystagmus, are crucial in predicting long-term outcomes in childhood glaucoma.