Development of a novel SupraChoroidal-to-Optic-NervE (SCONE) drug delivery system.

PURPOSE: Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique. METHODS: Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo. RESULTS: Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye. CONCLUSIONS: SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies. TRANSLATIONAL RELEVANCE: Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies.

Microglia depletion leads to increased susceptibility to ocular hypertension-dependent glaucoma.

In recent years, microglia have been highlighted for playing integral roles in neurodegenerative diseases, like glaucoma. To better understand the role of microglia during chronic ocular hypertension, we depleted microglia from aged (9-12 months old) DBA/2 J (D2) mice, which exhibit age-related increases in intraocular pressure, using a dietary CSF1R antagonist, PLX5622. Retinal ganglion cell (RGC) somas were counted, and optic nerve cross-sections stained and assessed for glaucomatous damage. Sustained administration of dietary PLX5622 significantly reduced the numbers of retinal microglia. Dietary PLX5622 did not lead to changes in intraocular pressure in D2 or normotensive DBA/2 J-Gpnmb+ (D2-Gpnmb+ ) control mice. While PLX5622-treated D2-Gpnmb+ did not develop optic nerve damage, PLX5622-treated D2 mice showed a significant increase in moderate-to-severe optic nerve damage compared to D2 mice fed a control diet. In conclusion, global reduction of microglia exacerbated glaucomatous neurodegeneration in D2 mice suggesting microglia play an overall beneficial role in protecting from ocular hypertension associated RGC loss.

Optic nerve compression associated with visual cortex functional alteration in dysthyroid optic neuropathy: A combined orbital and brain imaging study.

AIMS: To investigate the alterations of the optic nerve and visual cortex in dysthyroid optic neuropathy (DON), a subgroup of thyroid eye disease (TED). METHODS: Multiple orbital imaging biomarkers related to optic nerve compression and the amplitude of low-frequency fluctuations (ALFF) of the brain were obtained from 47 patients with DON, 56 TED patients without DON (nDON), and 37 healthy controls (HC). Correlation analyses and diagnostic tests were implemented. RESULTS: Compared with HC, the nDON group showed alterations in orbital imaging biomarkers related to optic nerve compression in posterior segments, as well as ALFF of the right inferior temporal gyrus and left fusiform gyrus. DON differed from nDON group mainly in the modified muscle index of the posterior segment of optic nerve, and ALFF of orbital part of right superior frontal gyrus, right hippocampus, and right superior temporal gyrus. Orbital and brain imaging biomarkers were significantly correlated with each other. Diagnostic models attained an area under a curve of 0.80 for the detection of DON. CONCLUSION: The combined orbital and brain imaging study revealed alterations of the visual pathway in patients with TED and DON as well as provided diagnostic value. The initiation of alterations in the visual cortex in TED may precede the onset of DON.

An Analysis of Optic Disc Parameters in Patients with Peripheral Retinal Tears Following Acute Posterior Vitreous Detachment: A Cross-Sectional Study.

Background: To investigate association between optic disc parameters analyzed by optical coherence tomography (OCT) and occurrence of peripheral retinal tears in patients with symptomatic posterior vitreous detachment (PVD). Methods: This cross-sectional study enrolled 75 patients with symptoms of acute PVD, who were allocated into two groups based on whether a peripheral retinal tear occurred or not. Results: When comparing the average retinal nerve fiber layer (RNFL) thickness (µm) between retinal tear and control groups, it was shown that patients with a retinal tear have a significantly higher (87.18 [95% confidence interval (CI), 84.47 to 89.9] vs 81.14 [95% CI, 77.81 to 84.46], P = 0.005) average RNFL thickness. Furthermore, we observed a significant difference (0.13, 0.06 to 0.22 vs 0.07, 0.04 to 0.1, P = 0.036, Mann-Whitney U-test) in the size of cup volume (mm3) between the tear and control groups, respectively. Linear regression showed a significant decrease (P = 0.029) in average RNFL thickness with increasing age, but without a significant difference between the two groups. There was no statistically significant difference between the tear and control groups in terms of rim area, disc area, and average cup-to-disc ratio. Conclusion: Patients with a higher average RNFL thickness and larger cup volume measured by OCT were more prone to develop a peripheral retinal tear. Increased peripapillary average RNFL thickness due to trauma and subsequent inflammation, possibly related to the more adherent posterior hyaloid membrane to the retina, may also indicate strengthened adhesions in the areas of the peripheral retina where retinal tears occur. OCT analysis of the optic nerve head may be used in everyday clinical practice as a predictor of the development of peripheral retinal tears in patients with symptomatic PVD.

Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

Whole-eye transplantation: Current challenges and future perspectives.

Whole-eye transplantation emerges as a frontier in ophthalmology, promising a transformative approach to irreversible blindness. Despite advancements, formidable challenges persist. Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival. Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive, prompting the exploration of neurotrophic support and immunomodulatory interventions. Immunological tolerance, paramount for graft acceptance, confronts the distinctive immunogenicity of ocular tissues, driving research into targeted immunosuppression strategies. Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks. Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities. Biomaterials, stem cell therapies, and precision immunomodulation represent promising avenues in this pursuit. Ultimately, the aim of this review is to critically assess the current landscape of whole-eye transplantation, elucidating the challenges and advancements while delineating future directions for research and clinical practice. Through concerted efforts, whole-eye transplantation stands to revolutionize ophthalmic care, offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

Case report: Bilateral optic nerve sheath meningocele: clinical aspects.

Optic nerve sheath meningocele is an enlargement of the sheath itself, consisting of a collection of cerebrospinal fluid along the perineural space. It should be considered primary if it is not associated with orbital-cerebral neoplasm or with cranio-orbital junction malformations. We report three cases of bilateral primary idiopathic optic nerve sheath meningocele, two of them with gradual vision loss. The first case presented a history of monocular blurred vision of the right eye and headache. It was initially treated with acetazolamide without any improvement, after which optic nerve sheath fenestration was required. The second case showed intermittent binocular diplopia with central 24-2 perimetry defects in the left eye. The third case was first presented as a subacute bilateral conjunctivitis with a suspected orbital pseudotumor. An incidental bilateral optic nerve sheath meningocele was found in the orbital imaging, being totally asymptomatic. In all the cases, orbital and cranial magnetic resonance with contrast and fat suppression was crucial in the diagnosis.

Prediction of the Cause of Glaucoma Disease Identified by Glaucoma Optical Coherence Tomography Test in Relation to Diabetes and Hypertension at a National Hospital in Seoul: A Retrospective Study.

Glaucoma remains the primary cause of long-term blindness. While diabetes mellitus (DM) and hypertension (HTN) are known to influence glaucoma, other factors such as age and sex may be involved. In this retrospective study, we aimed to investigate the associations between age, sex, DM, HTN, and glaucoma risk. We employed optical coherence tomography (OCT) conducted using a 200 × 200-pixel optic cube (Cirrus HD OCT 6000, version 10.0; Carl Zeiss Meditec, Dublin, CA, USA). Effects obscured by low-test signals were disregarded. Data were amassed from 1337 patients. Among them, 218 and 402 patients had DM and HTN, respectively, with 133 (10%) exhibiting both. A sex-based comparison revealed slightly greater retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness in females. Patients without DM and HTN were predominantly in their 50 s and 60 s, whereas DM and HTN were most prevalent in those in their 60 s and 70 s. Both RNFL and GCIPL thicknesses decreased with advancing age in most patients. The study revealed that older individuals were more prone to glaucoma than younger individuals, with a higher incidence among patients with DM and HTN and reduced RNFL and GCIPL thicknesses. Furthermore, early detection before advancing age could furnish valuable preventive insights.

Ophthalmic findings in the KIF1A-associated neurological disorder (KAND).

PURPOSE: To define the ophthalmic manifestations in KIF1A-associated neurological disorder (KAND), a rare, progressive neurodegenerative disorder caused by pathogenic variants in the KIFA1 gene. DESIGN: Cross-sectional study. METHODS: Clinical ophthalmic examination and multimodal imaging were performed for 24 participants enrolled in the KIF1AOutcome measures, Assessments, Longitudinal And endpoints (KOALA) Study. Visual evoked potentials (VEP) were performed on select participants. RESULTS: The average central visual acuity in pediatric participants was 20/43 (logMAR 0.329, range 0.0-1.0), and 20/119 (logMAR 0.773, range 0.471-1.351) in adults. Ninety-five percent of participants examined had some degree of optic nerve atrophy detected by clinical examination and/or optical coherence tomography (OCT). Almost forty percent had strabismus. Color vision, visual fields and stereopsis were impaired in most participants who were able to participate in testing. VEP showed varying degrees of signal slowing and diffuseness. CONCLUSIONS: Optic nerve atrophy is the primary ocular finding in individuals with KAND and is present at higher prevalence than previously reported. The degree of the atrophy is likely dependent on the severity of the pathogenic variant and possibly the age of the patient. Adults had worse vision on average than children, suggesting possible decline in vision with age. Strabismus in this cohort was common. Visual evoked potentials showed findings consistent with optic neuropathy and visual dysfunction even in the absence of obvious structural changes on OCT. Families should be counseled regarding visual impairment in KAND patients, so as to obtain appropriate support and assistance to maximize safety, functionality, and learning.

Comparison of Optic Nerve Sheath Diameter (ONSD) Measurements Obtained from USG Before and After Placement of Ventriculoperitoneal Shunt in Obstructive Hydrocephalus as a Surrogate Marker for Adequacy of Shunt Function: A Prospective Observational Study.

Introduction Optic nerve sheath diameter (ONSD) measured using ultrasonography has been widely used as a surrogate marker of elevated intracranial pressure. However, literature is sparse on the correlation between ONSD and ventriculoperitoneal (VP) shunt function, especially in adults with hydrocephalus. Our study was designed to assess the correlation between ONSD measured using ultrasonography before and 12 hours after VP shunt placement and the success of VP shunt placement assessed using computed tomography (CT) of the brain. Materials and Methods Fifty-one patients between 16 and 60 years of age, with obstructive hydrocephalus scheduled for VP shunt surgery were included in this prospective, observational study. ONSD measurements were obtained from both eyes prior to induction of anesthesia, immediately after the surgery, and at 6, 12, and 24 hours after the surgery. An average of three readings was obtained from each eye. Cerebrospinal fluid (CSF) opening pressure was noted after entry into the lateral ventricle. Noncontrast CT (NCCT) brain was obtained 12 hours after the surgery and was interpreted by the same neurosurgeon for signs of successful VP shunt placement. Results There was a significant reduction in ONSD in the postoperative period compared to ONSD measured preoperatively. The average ONSD (mean ± standard deviation) measured prior to induction of anesthesia, immediately after the surgery, and at 6, 12, and 24 hours after the surgery was 5.71 ± 0.95, 5.20 ± 0.84, 5.06 ± 0.79, 4.90 ± 0.79, and 4.76 ± 0.75 mm, respectively. The mean CSF opening pressure was 19.6 ± 6.9 mm Hg. Postoperative NCCT brain revealed misplacement of the shunt tip in only one patient. Conclusion ONSD measured using ultrasonography may be used as a reliable indicator of VP shunt function in adults with obstructive hydrocephalus.

Stabilizing axin leads to optic nerve hypoplasia in a mouse model of autism.

Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.

Acute-Onset Blindness in a Patient Diagnosed With Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOG-AD): A Case Report.

Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) poses a diagnostic challenge, often masquerading as other neurological disorders such as multiple sclerosis and aquaporin-4-positive neuromyelitis optica spectrum disorder. The deceptive clinical similarities demand a nuanced approach to differentiate these conditions effectively. This entails an extensive evaluation encompassing a meticulous medical history, advanced magnetic resonance imaging (MRI), cerebrospinal fluid analysis, and serum studies. In this context, we present a compelling case involving a 28-year-old Hispanic female with a history of migraine headache. She sought medical attention due to acute peripheral vision loss, ultimately diagnosed as MOG-AD through a comprehensive clinical assessment coupled with specific diagnostic tests. This case underscores the critical importance of precision in diagnostic procedures to ensure accurate identification and subsequent tailored treatment for MOG-AD, avoiding potential pitfalls associated with its resemblance to other neurological disorders.

Measurement of Optic Nerve Sheath Diameter by Bedside Ultrasound in Patients With Traumatic Brain Injury Presenting to Emergency Department: A Review.

The aim of this review article is to outline the effectiveness of using bedside ultrasound to measure the optic nerve sheath diameter (ONSD) in order to identify variations in intracranial pressure (ICP) and subsequently avoid the complication of secondary brain injury in patients with traumatic brain injury (TBI), who are admitted to an emergency department (ED). Reputable publications and numerous studies demonstrate the problem's exponential rampancy and pervasiveness. In a TBI patient, the emergence of secondary brain damage has been recognized as a serious emergency. It is believed that secondary brain damage is caused by an abnormally high ICP. High levels of ICP can be measured using both invasive and non-invasive approaches. ONSD measurement via bedside ultrasound has been identified as a quick, useful technique to be used in the ED to avoid potential morbidity and mortality owing to secondary brain injury.

Endoscopic endonasal optic nerve decompression in children younger than 2 years old with congenital optic canal stenosis: illustrative cases.

BACKGROUND: Congenital optic canal stenosis causing compressive optic neuropathy is a rare disorder that presents unique diagnostic and treatment challenges. Endoscopic endonasal optic nerve decompression (EOND) has been described for optic nerve compression in adults and adolescents but has never been reported for young children without pneumatized sphenoid sinuses. The authors describe preoperative and intraoperative considerations for three patients younger than 2 years of age with congenital optic canal stenosis due to genetically confirmed osteopetrosis or chondrodysplasia. OBSERVATIONS: Serial ophthalmological examinations, with a particular focus on object tracking ability, fundoscopic examination, and visual evoked potential trends in preverbal children, are important for detecting progressive optic neuropathy. The lack of pneumatization of the sphenoid sinus presents unique challenges and requires the surgical creation of a sphenoid sinus with the use of neuronavigation to determine the limits of bony exposure given the lack of easily identifiable anatomical landmarks such as the opticocarotid recess. There were no perioperative complications. LESSONS: EOND for congenital optic canal stenosis is safe and technically feasible even given the lack of pneumatization of the sphenoid sinus in young patients. The key operative step is surgically creating the sphenoid sinus through careful bony removal with the aid of neuronavigation. https://thejns.org/doi/10.3171/CASE23559.

Optic nerve decompression through pterional and supraorbital approaches in the treatment of severe traumatic optic neuropathy.

To investigate the effectiveness of optic nerve decompression (OND) in the treatment of severe traumatic optic neuropathy (TON) through pterional and supraorbital approaches, and to identify the prognostic factor for postoperative visual acuity (VA) following OND. Patients with severe TON treated with OND through either pterional or supraorbital approach in our institute from September 2019 to June 2022 were retrospectively reviewed in this study. Demographic information, trauma factors, the interval between trauma and complete blindness, the interval between trauma and surgery, and the associated craniofacial traumas were recorded. Hospitalization days and the postoperative VA of patients in two groups were compared. There were 54 severe TON patients with NLP included in this study; 21 patients underwent OND through the pterional approach, and the other 33 underwent the supraorbital approach. Respectively, in groups of pterional and supraorbital approaches, the average hospitalization days were 9.8 ± 3.2 and 10.7 ± 2.9 days (p = 0.58), the mean durations of follow-up were 18.9 ± 4.3 and 20.8 ± 3.7 months (p = 0.09), and the average circumference of OND were 53.14 ± 15.89 ◦ (range 220 ◦ -278◦) and 181.70 ± 6.56◦ (range 173 ◦ -193◦) (p<0.001). The overall improvement rates of pterional and supraorbital approaches are 57.1% and 45.5% (p = 0.40), respectively. Optic canal fracture (OCF) was revealed to be significantly associated with postoperative VA in the supraorbital approach (Binary: p = 0.014, CI: 1.573-57.087; Ordinal: p = 0.003, CI: 1.517-5.503), but not in the pterional approach. In the group of supraorbital approach, patients with OFC had a higher rate of a better outcome (78.6%) than those without (21.4%). Patients with severe traumatic TON may benefit from OND through either the pterional or supraorbital approach. OCF is a potential prognostic factor for postoperative VA following OND through the supraorbital approach.

Optimized Lipidomics Extraction of Sphingosine and Sphinganine from Optic Nerve for Signaling Studies.

Interconvertible sphingolipid metabolites represent germane constituents of eukaryotic membranes and are vital in the regulation of cellular homeostasis, proliferation, survival, and induction of autophagy. This protocol describes a step-by-step method for extractions of sphingosine and sphinganine from mammalian tissue samples, particularly from the murine optic nerve. These lipids are partitioned into a binary mixture of chloroform and methanol in a modified Bligh and Dyer method. This is followed with reverse phase ultrahigh-performance liquid chromatography fractionation with a C18+ column and subsequent tandem mass spectrometry (UHPLC-MS-MS) analysis of the biological abundance. These free sphingoid bases dissociate to form structurally distinctive carbocation product ions that can be confirmed with annotations of lipidomic databases or in-house fragmentation software.

Quantitative assessment of colour fundus photography in hyperopia children based on artificial intelligence.

OBJECTIVES: This study aimed to quantitatively evaluate optic nerve head and retinal vascular parameters in children with hyperopia in relation to age and spherical equivalent refraction (SER) using artificial intelligence (AI)-based analysis of colour fundus photographs (CFP). METHODS AND ANALYSIS: This cross-sectional study included 324 children with hyperopia aged 3-12 years. Participants were divided into low hyperopia (SER+0.5 D to+2.0 D) and moderate-to-high hyperopia (SER≥+2.0 D) groups. Fundus parameters, such as optic disc area and mean vessel diameter, were automatically and quantitatively detected using AI. Significant variables (p<0.05) in the univariate analysis were included in a stepwise multiple linear regression. RESULTS: Overall, 324 children were included, 172 with low and 152 with moderate-to-high hyperopia. The median optic disc area and vessel diameter were 1.42 mm2 and 65.09 µm, respectively. Children with high hyperopia had larger superior neuroretinal rim (NRR) width and larger vessel diameter than those with low and moderate hyperopia. In the univariate analysis, axial length was significantly associated with smaller superior NRR width (ß=-3.030, p<0.001), smaller temporal NRR width (ß=-1.469, p=0.020) and smaller vessel diameter (ß=-0.076, p<0.001). A mild inverse correlation was observed between the optic disc area and vertical disc diameter with age. CONCLUSION: AI-based CFP analysis showed that children with high hyperopia had larger mean vessel diameter but smaller vertical cup-to-disc ratio than those with low hyperopia. This suggests that AI can provide quantitative data on fundus parameters in children with hyperopia.

Comparative analysis of Krüppel-like factors expression in the retinas of zebrafish and mice during development and after injury.

The Krüppel-like factors (KLFs) have emerged as important transcriptional regulators of various cellular processes, including neural development. Some of them have been described as intrinsic factors involved in axon regeneration in the central nervous system (CNS) of vertebrates. Zebrafish are known for their ability to regenerate several tissues in adulthood, including the CNS, a capability lost during vertebrate evolution and absent in adult mammals. The role that KLFs could play in this differential ability remains unknown. Therefore, in this study, we analyzed the endogenous response of certain KLFs implicated in axon regeneration (KLFs 6, 7, 9, and 13) during retina development and after axon injury. The results showed that the expression of Klfs 6, 7, and 13 decreases in the developing retina of mice but not in zebrafish, while the mRNA levels of Klf9 strongly increase in both species. The response to injury was further analyzed using optic nerve crush (ONC) as a model of lesion. Our analysis during the acute phase (hours) demonstrated an induction of Klfs 6 and 7 expression exclusively in the zebrafish retina, while Klfs 9 and 13 mRNA levels increased in both species. Further analysis of the chronic response (days) showed that mRNA levels of Klf6 transiently increase in the retinas of both zebrafish and mice, whereas those of Klf7 decrease later after optic nerve injury. In addition, the analysis revealed that the expression of Klf9 decreases, while that of Klf13 increases in the retinas of zebrafish in response to optic nerve injury but remains unaltered in mice. Altogether, these findings support the hypothesis that KLFs may play a role in the differential axon regeneration abilities exhibited by fish and mice.

Intermediate-Term Outcomes of Ahmed Glaucoma Valve Implantation for Uveitic Glaucoma: A Tertiary Centre Experience.

PURPOSE: To present the outcomes of Ahmed glaucoma valve (AGV) implantation in uveitic glaucoma (UG) in a tertiary eye center in Riyadh, Saudi Arabia. METHODS: A retrospective review of all UG patients who underwent AGV implantation at a single, tertiary care eye center from January 2008 to December 2018. The main outcome measures were change in mean intraocular pressure (IOP), number of antiglaucoma medications, overall success rate in different follow-up periods, complete and qualified success from last follow up, and complications. The success of the treatment was defined as patients achieving intraocular pressure (IOP) levels between 6- and 21-mm Hg with or without additional antiglaucoma medications and/or a minimum of 20% reduction from baseline IOP. RESULTS: The study included 74 patients (86 eyes), with a mean follow-up of 4.9 ± 2.9 years. The mean IOP was 32.2 ± 8.5 mmHg at baseline and 16.3 ± 6.6 mmHg at the last follow-up (p < 0.001). The mean number of antiglaucoma medications decreased from 3.5 ± 0.7 preoperatively to 1.3 ± 1.4 at the last follow-up (p < 0.001). Overall survival rates at 1, 3, 5, and 10 years were 96.5%, 92.7%, 91%, and 56.9%, respectively. Complete and qualified success rates were 37.9% and 48.3% at the end of follow up, respectively. The rate of postoperative complications was 56%, of which 18 eyes (20%) required surgical revision. Bivariate Cox proportional hazards regression analysis did not reveal any factors significantly associated with failure. CONCLUSIONS: AGV is safe and effective in providing intermediate-term IOP control in UG patients. Complications reported in our cohort were mostly transient and conservatively treated.

Values of peripapillary retinal nerve fibre layer thickness are different in children and adults.

CLINICAL RELEVANCE: The detection of abnormal values of peripapillary nerve fibre layer (pRNFL) thickness measured with optical coherence tomography (OCT) is important for detecting optic nerve disease in children. BACKGROUND: To evaluate the level of agreement between the adult reference database supplied with an OCT device and the present paediatric study database for the measurement of pRNFL thickness in children. This study also aimed to provide reference values for pRNFL thickness according to the spherical equivalent in the paediatric population. METHODS: This was a cross-sectional study. One hundred and twenty-six healthy children were included, who had undergone a full ophthalmological examination including cycloplegic refraction and examination of pRNFL thickness using the Topcon 3D OCT 2000 device (Topcon Corporation, Tokyo, Japan). Values equal to or below the fifth percentile (≤p5) and above the 95th percentile (>p95) were considered abnormal. Observed agreement and specific agreement were investigated between OCT measurements classified with paediatric and adult reference values for normality. RESULTS: Values ≤ p5 in the adult database were recorded for 2 of the 30 values (6.6%) of the pRNFL values by quadrants ≤p5 in the paediatric database and 17 of the 88 (19.3%) values by sectors ≤p5. For values >p95 in the adult database, 88% by quadrants and 72% by sectors would have been classified as being within the normal range using the paediatric database. CONCLUSION: The use of adult reference values currently available in OCT devices can lead to classification errors concerning the normal range of pRNFL thickness in a large proportion of paediatric patients. The use of normative paediatric databases, such as the one discussed in this study, should be taken into consideration.