l-Serine Protects Murine Retinal Ganglion Cells from Oxidative Stress via Modulation of Mitochondrial Dysfunction.

PURPOSE: This study aimed to investigate the effects of l-serine on mitochondrial dysfunction in retinal ganglion cells after exposure to H2O2-induced oxidative stress. METHODS: Retinal ganglion cells obtained from C57BL6 mice (postnatal days 1-4) were purified and cultured. A cell viability assay was performed following exposure to H2O2-induced oxidative stress to assess the cytoprotective effects of l-serine on retinal ganglion cells. Flow cytometry with CellROX Deep Red and MitoSOX dyes was performed to analyze the cytoplasmic and mitochondrial reactive oxygen species levels, respectively. Staining with the fluorescent probe JC-1 was used to detect changes in the mitochondrial membrane potential. The oxygen consumption rate and Bioenergetic Health Index were used to evaluate mitochondrial respiration. RESULTS: H2O2 treatment was found to induce mitochondrial dysfunction in retinal ganglion cells. Pretreatment with l-serine prevented cytotoxicity and significantly increased the viability of retinal ganglion cells following exposure to H2O2-induced oxidative stress (p < .05). l-Serine alleviated reactive oxygen species production in retinal ganglion cells following exposure to H2O2-induced oxidative (p < .05). Further, it successfully mitigated H2O2-induced mitochondrial depolarization in retinal ganglion cells (p < .05) and significantly increased the oxygen consumption rate and Bioenergetic Health Index in retinal ganglion cells following exposure to H2O2-induced oxidative stress (p < .05). CONCLUSION: Pretreatment with l-serine protected retinal ganglion cells from H2O2-induced oxidative stress by improving mitochondrial function. The findings of the present study suggest that l-serine is a potential candidate for treatment of reactive oxygen species-related ocular diseases such as mitochondrial optic neuropathies.

Clinical Relevance of Plasma Prolylcarboxypeptidase Level in Patients with Idiopathic Acute Optic Neuritis.

Objectives: This study evaluated the plasma concentration of prolylcarboxypeptidase (PRCP) and its clinical relevance in patients with idiopathic acute optic neuritis (ON). Methods: We investigated the expression of PRCP in the optic nerves of experimental autoimmune optic neuritis (EAON)-induced mice. Peripheral blood samples were collected from ON patients (n = 20) and healthy controls (n = 20). ELISA was used to measure the plasma PRCP levels. We performed measurements of visual acuity and the mean thicknesses of the macular ganglion cell layer plus inner plexiform layer (GCL+IPL) at diagnosis and 6 months after diagnosis. Results: The PRCP mRNA expression in EAON-induced mice was markedly higher than that in naïve mice. The mean plasma PRCP level was significantly higher in patients with ON than in controls. Plasma PRCP levels were negatively correlated with logMAR visual acuity at 6 months after diagnosis and differences in macular GCL+IPL thickness during an ON attack. A plasma PRCP level of 49.98 (pg/mL) predicted the recurrence of ON with a 75% sensitivity and 87.5% specificity. Conclusions: Patients with idiopathic acute ON had higher plasma PRCP levels, and this was positively correlated with final visual outcome and well-preserved macular GCL+IPL thickness during an ON attack. The increase in plasma PRCP level may reflect its compensatory secretion to counteract neuroinflammation in ON patients.

Sirtuin 3 mutation- induced mitochondrial dysfunction and optic neuropathy: a case report.

BACKGROUND: Mitochondrial optic neuropathy is characterized by painless, progressive, symmetrical central vision loss, and dyschromatopsia owing to mitochondrial dysfunction. This report documents a rare case of mitochondrial optic neuropathy due to the SIRT3 gene mutation. CASE PRESENTATION: This report describes a case of a 17-year-old boy who presented with symptoms of bilateral painless, progressive vision decline over several years. Fundus examination revealed temporal pallor of the optic nerve head in both the eyes and an OCT showed considerable thinning of the retinal nerve fiber and ganglion cell layers. Pathogenicity was confirmed by decreased mitochondrial function measured by bioenergetic health index and oxygen consumption rate in this patient. Subsequent NGS revealed a missense mutation of the SIRT3 gene (c.1137G > C, p.Trp379Cys) in the patient. CONCLUSIONS: This case describes the clinical manifestation of mitochondrial optic neuropathy due to the SIRT3 gene mutation.

Increased Plasma Lipocalin-2 Levels in Patients with Myelin Oligodendrocyte Glycoprotein-IgG-Positive Optic Neuritis.

This study aimed to evaluate the correlation between plasma lipocalin-2 (LCN2) levels and myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) seropositivity in patients with optic neuritis. Peripheral blood samples were collected from 19 patients with optic neuritis and 20 healthy controls. Plasma LCN2 and MOG-IgG levels were measured using enzyme-linked immunosorbent assay and a cell-based assay, respectively. The correlation between plasma LCN2 levels and MOG-IgG titers in patients with optic neuritis was analyzed. Receiver operating characteristic (ROC) curves were constructed to assess and compare the ability of plasma LCN2 and MOG-IgG levels for predicting optic neuritis recurrence. Patients with MOG-IgG-positive optic neuritis had significantly higher mean plasma LCN2 levels than controls and patients with MOG-IgG-negative optic neuritis (p = 0.037). Plasma LCN2 and MOG-IgG levels were significantly correlated in patients with optic neuritis (r = 0.553, p = 0.0141). There were no significant differences in the areas under the ROC curve (AUC) of plasma LCN2 (0.693, 95% confidence interval [CI] 0.443-0.880, p = 0.133) and MOG-IgG (0.641, 95% CI, 0.400-0.840, p = 0.298) levels (95% CI, -0.266-0.448, p = 0.618). Plasma LCN2 levels may aid differentiation of MOG-IgG-positive optic neuritis from MOG-IgG-negative optic neuritis.

Protective Role of Limitrin in Experimental Autoimmune Optic Neuritis.

Purpose: This study investigated the role of limitrin in the pathogenesis of demyelinating optic neuritis using an experimental autoimmune optic neuritis (EAON) model. Methods: EAON was induced in mice via subcutaneous injection with myelin oligodendrocyte glycoprotein peptide. Limitrin protein and mRNA expression were examined in the optic nerve before and after EAON induction. Proinflammatory cytokine expression profiles and degree of glial activation were compared between wild-type (WT) and limitrin knockout mice by real-time PCR and histologic analysis, respectively, after EAON induction. Plasma limitrin levels in patients with optic neuritis and healthy controls were measured by ELISA. Results: Limitrin expression, observed in astrocytes in the optic nerve of WT mice, was lower in EAON-induced than in naïve WT mice. A comparative analysis of WT and limitrin knockout mice revealed that limitrin deficiency induced more severe neuroinflammation and glial hyperactivation in the optic nerve after EAON induction. Limitrin-deficient astrocytes were more chemotactically responsive to neuroinflammatory stimulation than WT astrocytes. Patients with optic neuritis demonstrated higher plasma limitrin levels than healthy controls (P = 0.0001), which was negatively correlated with visual acuity at the nadir of the optic neuritis attack (r = 0.46, P = 0.036). Conclusions: Limitrin deficiency induced severe neuroinflammation and reactive gliosis in the optic nerve after EAON induction. Our results imply that astrocyte-derived limitrin may protect against neuroinflammation by decreasing immune cell infiltration into the optic nerve. The plasma limitrin level may reflect the extent of blood-brain barrier disruption and provide a valuable biomarker reflecting the severity of optic neuritis.

Congenital abnormalities of the retinal vasculature in neurofibromatosis type I.

The aim of this cross-sectional study was to investigate congenital abnormalities of the retinal vasculature (CARVs) in patients with neurofibromatosis type I (NF-1). Forty-eight patients (96 eyes) with NF-1 diagnosed according to the National Institutes of Health (NIH) criteria and 48 healthy controls were included in this study. Standard fundus photographs were obtained for each subject to evaluate the presence and frequency of CARVs. The sensitivity, specificity, and diagnostic accuracy of different cut-off numbers of CARVs were compared with those of the NIH criteria. Forty-four (91.7%) patients in the NF-1 group demonstrated either supranumeraty optic disc vessels or triple branching of the retinal vasculature, and 22 patients (45.8%) demonstrated both findings. The frequencies of these two CARVs were significantly different between the two groups (p < 0.00001). A cut-off value of either one for supranumerary optic disc vessels or triple branching showed the highest accuracy along with sensitivity and specificity of 91.7% and 87.5%. CARVs such as supranumerary optic disc vessels or triple branching were frequently observed in NF-1 patients, and their occurrence was unrelated to the age of patients. Thus, these CARVs could be added as new ophthalmologic manifestions for NF-1 and may potentially enable early diagnosis of NF-1.

Heimann-Bielschowsky phenomenon and hypotropic DVD in case of monocular vision loss: a case report.

BACKGROUND: The Heimann-Bielschowsky phenomenon (HBP) is an underrecognized condition characterized by slow, pendular, vertical oscillations of the eye accompanying monocular vision loss. Hypotropic dissociated vertical deviation (DVD) is another rare condition induced by asymmetric visual input. This report documents a rare case of HBP with hypotropic DVD. CASE PRESENTATION: This report describes a case of a 58-year-old woman with HBP and hypotropic DVD, having suffered monocular vision loss in the left eye due to blunt trauma at the age of 10. Preoperatively, she was orthophoric at near fixation and demonstrated an intermittent, slow hypotropia of the left eye upon distance fixation that never rose above the midline. She underwent a 7 mm recession of the inferior rectus muscle in the left eye. After surgery, intermittent, downward drifts became constant vertical oscillations at both distance and near fixation. CONCLUSIONS: This case describes the clinical manifestation of an eye movement disorder related to prolonged monocular vision loss.

Comparison of surgical outcomes of slanted procedure for exotropia with convergence insufficiency according to their response to preoperative monocular occlusion.

The aim of this prospective study was to compare surgical outcomes of slanted bilateral lateral rectus (LR) recession for intermittent exotropia (IXT) with convergence insufficiency (CI) according to their response to preoperative monocular occlusion. This prospective study included 55 children who underwent slanted bilateral LR recession for IXT with CI. Patients were divided into two groups according to their response to preoperative monocular occlusion for 2 hours. The True CI group was defined as having near-distance differences of ≥10 PD before and after occlusion; the Masked CI group as having near-distance differences of <10 PD and ≥10 PD prior to and after occlusion. Slanted procedure reduced distance and near exodeviations from 32.1 PD and 43.0 PD to 3.5 PD and 4.4 PD, and collapsed near-distance differences from 10.9 PD to 1.0 PD at 3 years postoperatively. Cumulative probabilities of surgical success were 76%, and the mean recurrence was 50 months at 3 years postoperatively; the True CI and Masked CI groups showed cumulative success rates of 89% and 55%, respectively (p = 0.0052). Patients in the True CI group demonstrated surgical outcomes superior to those demonstrated by patients in the Masked CI group after slanted bilateral LR recession.

Surgical Responses and Outcomes of Bilateral Medial Rectus Recession in Esotropia With Spinocerebellar Ataxia.

PURPOSE: To evaluate the surgical responses and outcomes of bilateral medial rectus (BMR) recession in esotropic patients with spinocerebellar ataxia (SCA) and to compare the results with normal controls. METHODS: The medical records of patients with SCA who underwent strabismus surgery for esotropia between 2006 and 2015 were reviewed retrospectively. Five esotropic patients with SCA (SCA group) and 10 esotropic patients without neurologic disorders (control group) who underwent BMR recession were included. Success rates, surgical responses, and the amount of preoperative and postoperative distance-near disparity were evaluated and compared between the groups. RESULTS: The mean preoperative esodeviation was not different between the SCA and control groups (20 vs 17.3 prism diopters [PD], P = .214). However, patients with SCA showed significant undercorrection compared with controls 1 week postoperatively (4.8 vs 1.0 PD, P = .048) and at the final follow-up (6.8 vs 1.8 PD, P = .032). The surgical success rates for the SCA and control groups were 40% and 80%, respectively (P = .095). Patients with SCA demonstrated a significantly reduced surgical response compared with controls (3.15 vs 3.87 PD/mm, P = .004), and a greater amount of postoperative distance-near disparity than controls (8.0 vs 1.1 PD, P = .001). CONCLUSIONS: A significant undercorrection was observed following BMR recession in esotropic patients with SCA. Accordingly, the authors recommend a slight overcorrection of 5 to 10 PD or adding a slanting procedure when planning strabismus surgery for this distinct group of patients. [J Pediatr Ophthalmol Strabismus. 2019;56(4):266-270.].

A family with a mild form of congenital nystagmus and optic disc coloboma caused by a novel PAX6 mutation.

Congenital nystagmus (CN) is a heterogeneous disease that shows variable clinical features. There are a few mutations that are known to cause CN. Among them, a PAX6 mutation is known to cause CN with an extremely high frequency of aniridia. Here, we report on a family with an autosomal dominant PAX6 mutation, c.214G > A (p.Gly72Ser.), who presented with CN in the absence of aniridia. This study describes detailed clinical findings, including videonystagmography and fundus photography findings and emphasizes the importance of screening for the PAX6 gene in patients who present with CN in the absence of aniridia, as this will further elucidate the known phenotypes of PAX6-related diseases.

Myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.

PURPOSE OF REVIEW: Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated optic neuritis has been established as a new entity of optic neuropathy. We will review recent advances in pathophysiology, diagnosis, and clinical manifestations of MOG-IgG-associated optic neuritis to better understand its distinctive characteristics. RECENT FINDINGS: MOG is expressed on the surface of myelin sheaths and oligodendrocytes. MOG is highly immunogenic and is a potential target of inflammatory demyelinating disease. MOG-IgG activate immune responses and cause demyelination without astrocytopathy. MOG-IgG are measured by cell-based assays, which have higher sensitivity and specificity than ELISA. Patients with MOG-IgG-associated optic neuritis present with initially severe vision loss, are more likely to have optic disc edema, but have favorable visual outcomes. Furthermore, patients with MOG-IgG-associated optic neuritis have higher rates of recurrence compared with MOG-IgG seronegative patients. MOG-IgG-associated optic neuritis responds well to steroid treatment, however, close monitoring for signs of relapse and long-term immunosuppression may be necessary. SUMMARY: MOG-IgG associated optic neuritis demonstrates distinctive pathophysiological and clinical characteristics from optic neuritis in aquaporin4-IgG seropositive or multiple sclerosis patients. Measurements of MOG-IgG titers by cell-based assays will be helpful for the diagnosis and treatment of optic neuritis.

Vertical rectus muscle recession versus combined vertical and horizontal rectus muscle recession in patients with thyroid eye disease and hypotropia.

PURPOSE: To compare the postoperative vertical drift in patients with thyroid eye disease (TED) with hypotropia who underwent vertical rectus recession alone versus vertical rectus recession combined with horizontal rectus recession. METHODS: The medical records of patients with TED who underwent strabismus surgery for hypotropia between 2006 and 2015 were reviewed retrospectively. Patients were divided into two groups: group 1 underwent vertical rectus recession only; group 2 underwent vertical rectus recession plus horizontal rectus recession. Data collection included pre- and postoperative deviation measurements and amount of surgical recession performed. The amount of postoperative vertical drift between groups was compared. RESULTS: Of 67 patients who underwent surgery during the study period, 18 met inclusion criteria, 9 in each group. Mean postoperative hypotropia was 24.2Δ in group 1 and 24.5Δ in group 2 (P = 0.82). Mean vertical deviations were 0.3Δ and -2.2Δ (P = 0.134) on postoperative day 1; -0.9Δ and -8.0Δ (P = 0.043) at final follow-up for groups 1 and 2. Mean postoperative vertical drift toward hypertropia was 1.2Δ in group 1 and 6.8Δ in group 2 (P = 0.048). The surgical success rate for group 1 was superior to that for group 2 (89% vs 67% [P = 0.024]). CONCLUSIONS: There was a significantly larger postoperative vertical drift in TED patients with hypotropia who had combined vertical rectus and horizontal rectus recessions compared with those who underwent vertical rectus recession alone.

Comparison of the Thickness and Volume of the Macula and Fovea in Patients with Anisometropic Amblyopia Prior to and after Occlusion Therapy.

PURPOSE: To compare the thickness of superior, temporal, inferior, and nasal macula and foveal thickness and volume in patients with anisometropic amblyopia prior to and after successful occlusion therapy using optical coherence tomography (OCT) measurement. METHODS: Data were collected prospectively on 30 patients with unilateral anisometropic amblyopia from December 2006 to August 2007. All patients had anisometropia of 2.0 diopters or more. OCT scans were obtained for all patients at diagnosis. Occlusion therapy was then prescribed and OCT scans were obtained again at the time of successful occlusion therapy (defined as interocular difference of <0.1 log units). The Stratus OCT-3 was used to measure fovea thickness and volume and the thickness of superior, temporal, inferior, and nasal macula (within a diameter of 3 mm). RESULTS: Of 30 patients, 22 (mean age of 5.8 years) had successful resolution of amblyopia. The mean duration of occlusion was 11.24 months and mean best-corrected visual acuity at diagnosis was 0.35 ± 0.12 logarithm of the minimum angle of resolution. The mean thicknesses of the superior, temporal, inferior, and nasal macula prior to and after occlusion were not significantly different (p > 0.05). However, mean foveal volume prior to occlusion therapy (0.15 ± 0.02 mm³) decreased after occlusion (0.14 ± 0.01 mm³) with statistical significance (Wilcoxon signed rank test, p = 0.025). CONCLUSIONS: There was a meaningful decrease in foveal volume in patients with anisometropic amblyopia after successful occlusion therapy. Whether this decrease relates to visual improvement of the amblyopic eye remains to be determined.

Acute visual loss after botulinum toxin A injection in the masseter muscle.

PURPOSE: Acute visual loss after facial injection of cosmetic materials is rarely reported. In this study, we report one patient who developed acute visual loss after an injection of botulinum toxin A for esthetic purposes. METHODS: A 43-year-old Korean woman presented with a decrease in visual acuity to 20/800 after an injection of botulinum toxin A in the masseter muscle. The visual field testing showed an inferior altitudinal defect, and fluorescein angiography revealed a delayed arm-retinal circulation time. RESULTS: After intravenous and oral prednisolone was administered, the patient's visual acuity gradually improved. Two months after the botulinum toxin A injection, the visual acuity had almost returned to baseline, with a remaining paracentral scotoma. CONCLUSIONS: This is the first case of acute visual loss following an injection of botulinum toxin A in a facial lesion. This case emphasizes that the potential risks of botulinum toxin A injection should be considered, and the procedure should be performed delicately.

Cryopreserved rabbit amniotic membrane alleviated inflammatory response and fibrosis following experimental strabismus surgery in rabbits.

We evaluate the ability of cryopreserved rabbit amniotic membrane (AM) transplantation to reduce postoperative inflammation and the extent of fibrosis following experimental strabismus surgery. Ten white rabbits underwent bilateral superior rectus (SR) muscle resection. In the left eye, the resected SR muscle was wrapped with cryopreserved rabbit AM. The right eye underwent SR resection only and served as a control. The eyes were enucleated 4 weeks after strabismus surgery. The degree of postoperative inflammatory infiltration, the extent of fibrosis, and profile of the relative expression of inflammatory mediators in the SR muscle were evaluated and compared between the two groups by histological analysis and real-time polymerase chain reaction (PCR). There were statistically meaningful differences in the degree of postoperative inflammatory infiltration and extent of fibrosis between the eyes treated with cryopreserved rabbit AM after SR resection and those underwent SR resection only. A significant decrease in the expression of inflammatory cytokines [interleukin (IL)-12a, IL-12b, IL-17f, and tumor necrosis factor- alpha (TNF-α)], and a markedly increased expression of anti-inflammatory cytokines (transforming growth factor-beta-1(TGFß-1) and IL-10) were observed in the eyes treated with cryopreserved rabbit AM. In this study, we demonstrate that cryopreserved rabbit AM is effective in reducing postoperative inflammation and extent of fibrosis in a rabbit model of strabismus surgery. Our results imply that cryopreserved AM allograft has anti-inflammatory and anti-scarring properties that can prevent postoperative adhesions following strabismus surgery.

Dominant Optic Atrophy and Leber's Hereditary Optic Neuropathy: Update on Clinical Features and Current Therapeutic Approaches.

Dominant optic atrophy (DOA) and Leber hereditary optic neuropathy (LHON) are the two most common inherited optic neuropathies encountered in clinical practice. This review provides a summary of recent advances in the understanding of the clinical manifestations, current treatments, and ongoing clinical trials of these two optic neuropathies. Substantial progress has been made in the understanding of the clinical, genetic, and pathophysiological basis of DOA and LHON. Pathogenic OPA1 gene mutations in DOA and 3 primary mutations of mitochondrial DNA in LHON-induced mitochondrial dysfunction, which in turn leads to increased reactive oxygen species levels in mitochondria and possibly insufficient ATP production. The pathologic hallmark of these inherited optic neuropathies is primary degeneration of retinal ganglion cells, preferentially in the papillomacular bundle, which results in temporal optic disc pallor and central or cecocentral visual loss. There are no effective treatments for patients with LHON and DOA, although clinical trials are underway for the former. Translational research for these diseases is entering an accelerated phase with the availability of animal models, and a variety of pharmacological and genetic therapies are being developed.

Advances in experimental optic nerve regeneration.

PURPOSE OF REVIEW: Recent advances in experimental studies of optic nerve regeneration to better understand the pathophysiology of axon regrowth and provide insights into the future treatment of numerous optic neuropathies. RECENT FINDINGS: The optic nerve is part of the central nervous system and cannot regenerate if injured. There are several steps that regenerating axons of retinal ganglion cells (RGCs) must take following optic nerve injury that include: maximizing the intrinsic growth capacity of RGCs, overcoming the extrinsic growth-inhibitory environment of the optic nerve, and optimizing the reinnervation of regenerated axons to their targets in the brain. Recently, some degree of experimental optic nerve regeneration has been achieved by factors associated with inducing intraocular inflammation, providing exogenous neurotrophic factors, reactivating intrinsic growth capacity of mature RGCs, or by modifying the extrinsic growth-inhibitory environment of the optic nerve. In some experiments, regenerating axons have been shown to reinnervate their central targets in the brain. SUMMARY: Further approaches to the combination of aforementioned treatments will be necessary to develop future therapeutic strategy to promote ultimate regeneration of the optic nerve and functional vision recovery after optic nerve injury.

Clinical Analysis of Ocular Parameters Contributing to Intraoperative Pain during Standard Phacoemulsification.

Purpose. To study the correlation between ocular parameters and subjective pain that patients perceived during phacoemulsification. Methods. Medical records of 142 patients who underwent standard phacoemulsification under topical anesthesia between March and August 2016 were retrospectively reviewed. The pain during phacoemulsification and 1 h after surgery was assessed and compared using a visual analog scale. In addition, demographic data, preoperative biometric parameters, and intraoperative surgical parameters were recorded. Results. Mean age of patients was 67.49 ± 12.50 years. The mean pain score was 2.26 ± 0.85 during phacoemulsification and 0.40 ± 0.69 postoperatively. Intraoperative pain was significantly associated with higher preoperative intraocular pressure (ß = 0.220, P = 0.016), greater anterior chamber depth (ß = 0.210, P = 0.028), and greater axial length (ß = 0.181, P = 0.043). Conclusions. To reduce the subjective pain when patients have high preoperative intraocular pressure, large anterior chamber depth, or great axial length, supplementary procedures may be required.