[Leber's hereditary optic neuropathy].

Leber's hereditary optic atrophy (LHON) is a genetic optic neuropathy that is more prevalent in young males but can occur from childhood to old age. The primary cause is mitochondrial genetic mutations, which are associated with dysfunction of mitochondrial electron transport chain complex I. It manifests as acute to subacute visual impairment, often starting unilaterally but progressing to involve both eyes within weeks to months. Visual loss is severe, with many patients having corrected visual acuity below 0.1. The differential diagnosis of optic neuritis is essential, and assessments such as pupillary light reflex, fluorescein fundus angiography, and magnetic resonance imaging can be useful for differentiation. LHON should be considered as one of the differential diagnoses for optic neuritis, and collaboration between neurologists and ophthalmologists is crucial for accurate diagnosis and appropriate treatment.

Evaluation of Steroid Pulse Therapy Responsiveness in Myelin-Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis.

PURPOSE: Myelin-oligodendrocyte glycoprotein antibody-positive optic neuritis (MOGON) is usually responsive to the steroid, but, for some patients, steroid pulse therapy alone may be inadequate. This study aimed to investigate the factors predicting the response to steroid pulse therapy in MOGON. METHODS: This study included 17 patients (24 eyes) with MOGON, who received single steroid pulse therapy as initial treatment. Best corrected visual acuity (BCVA) and mean deviation (MD) values after treatment were examined concerning findings at onset. RESULTS: No correlation was found between BCVA at onset and after treatment, but a correlation was observed between MD values at onset and after treatment (correlation coefficient 0.48, p=0.01, Spearman's rank correlation coefficient). Age, gender, duration from onset to treatment, magnetic resonance imaging findings, and optical coherence tomography findings did not affect visual function after treatment. CONCLUSIONS: Severe visual field impairment at onset may indicate that additional treatment may be necessary.

Clinical Features and Prognostic Factors in Anti-Myelin Oligodendrocyte Glycoprotein Antibody Positive Optic Neuritis.

In order to review the clinical features of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis (MOGON), we investigated the clinical characteristics, visual function, optical coherence tomography findings, and magnetic resonance imaging of 31 patients (44 eyes). MOGON was more common in middle age without sex difference and was characterised by pain on eye movement and optic disc swelling. Magnetic resonance imaging lesions tended to be long with inflammation around the optic nerve sheath; longer lesions were associated with worse visual acuities at onset. Recurrence was significantly associated with retinal nerve fibre layer thinning, and thus, it is important to reduce recurrence as much as possible.

A Japanese Case of Leber's Hereditary Optic Neuropathy with the m.13051G>A Pathogenic Variant.

Leber's hereditary optic neuropathy (LHON) is one of the hereditary optic neuropathies and is principally caused by three frequent mitochondria deoxyribonucleic acid (DNA) pathogenic variants (m.11778 G>A, m.3460 G>A, and m.14484T>C). These pathogenic variants account for 90% of LHON cases, with rare pathogenic variants accounting for the remaining cases. We report the first Japanese case of LHON with the m.13051 G>A pathogenic variant, which is a rare primary pathogenic variant of LHON. A 24-year-old woman developed subacute visual loss in both eyes over several months. The best corrected visual acuity (BCVA) was 6/120 in her right eye (OD) and 6/7.5 in her left eye (OS). A relative afferent pupillary defect was not detected. Humphrey visual field testing revealed a central scotoma OD and a temporal paracentral scotoma OS. Fundus examination showed the presence of a pale optic disc OD and optic disc swelling with peripapillary microangiopathy OS. Orbital magnetic resonance imaging showed no abnormal findings. As the mitochondrial DNA gene testing demonstrated the m.13051 G>A pathogenic variant, the patient was diagnosed with LHON. Subsequently, her BCVA worsened to 6/600 in each eye, followed by a nearly plateau-like progression thereafter. This mutation has been primarily reported in Europe but has not yet been confirmed in the Asian region. This case also indicates the importance of examining the whole mitochondrial DNA gene for pathogenic variants in cases where one of the three major pathogenic variants has not been not detected.

Effect of the COVID-19 pandemic lockdown on the physique of school-age children in Japan.

PURPOSE: Schools in Japan were closed nationwide from March to May 2020 because of the coronavirus disease 2019 (COVID-19) pandemic. Many suspect that this school closure affected children's mental and physical health. We investigated changes in school-age children's physiques to determine the effects of the COVID-19 lockdown and restrictions on their health. METHODS: Data were extracted from a database of school physical examinations in Osaka elementary and junior high schools for 4 consecutive years from 2018 to 2021. The following characteristics were analyzed: short stature, tall stature, underweight, mild obesity, middle grade obesity, and severe obesity. The paired Student t-test was used to compare school examination data in the prepandemic period (2018-2019), pandemic lockdown (2019-2020), and post-lockdown period (2020-2021). RESULTS: Obesity rates in elementary school students aged 6-12 years, particularly in boys, were significantly higher during the lockdown than they were in 2019. After the pandemic, the tall stature rate continued to rise, while rates of short stature and underweight decreased in both sexes in 2020. In junior high school students aged 12-15 years, rates of obesity and underweight tended to decrease in 2020. However, these rates rebounded and rose in 2021 when the lockdown was lifted. CONCLUSION: During the COVID-19 pandemic lockdown, elementary school students gained weight, while junior high school students lost weight. The lockdown that was implemented during the COVID-19 pandemic had an unfavorable effect on weight gain, particularly in young school-age children.

A Case of Herpes Zoster Ophthalmicus With Multiple Delayed Ocular Complications.

Herpes zoster ophthalmicus (HZO) presents a variety of ocular complications, most of which occur simultaneously as skin lesions. We report a case of HZO with delayed onset of multiple ocular complications. A 72-year-old man developed HZO, blepharitis, iritis, and conjunctivitis in the left eye, which resolved after topical ocular treatment and systemic acyclovir administration. However, six weeks after the first onset of the rash, the patient came to our hospital because of recurrent blepharitis, iritis, scleritis, conjunctivitis, eye pain, ptosis, and blurred vision in the left eye. Best corrected visual acuity (BCVA) in the left eye had decreased to hand motion, and the Goldmann visual field test showed only mild residual peripheral vision on the lateral side. Intraocular pressure showed 25 mmHg in the left eye and inflammation in the anterior chamber with paralytic mydriasis. Orbital magnetic resonance imaging (MRI) showed the contrast effects with the lacrimal gland, superior ophthalmic vein, supraorbital nerve, optic nerve, and around optic nerve sheath. The patient was diagnosed with optic neuritis, optic perineuritis, ptosis, paralytic mydriasis, trigeminal neuralgia, lacrimal gland inflammation, blepharitis, iritis, scleritis, and ocular hypertension after HZO, and three courses of steroid pulse therapy were administered. Thereafter, BCVA improved to 0.3 in the left eye, with improvement in central vision, and MRI lesions and other symptoms also improved. The patient has had no complications or recurrence of HZO. HZO can cause a variety of ocular complications. Since autoimmune mechanisms might be involved, combined immunotherapy should be considered.

A Case of Impending Central Retinal Vein Occlusion Associated With Antiphospholipid Antibody Syndrome Complicated by Paracentral Acute Intermediate Layer Maculopathy.

We report a case of impending central retinal vein occlusion (CRVO) due to antiphospholipid syndrome (APS) complicated by paracentral acute middle maculopathy (PAMM). A 42-year-old man with no medical history acutely presented with blurred vision in his right eye. The best-corrected visual acuity was 20/20 in the right eye, but the Goldman visual field test showed a dark spot over the superior nasal region of the right eye. Fundus examination showed dilated and tortuous retinal veins of the right eye with delayed filling of the inferior retinal veins on fluorescein angiography. Optical coherence tomography (OCT) showed a hyperreflective lesion confined to the inner nuclear layer (INL), consistent with PAMM. After several weeks, his symptoms improved, and the dilated retinal vein and the INL hyperreflexia on OCT were reduced. Multiple positive findings for anti-cardiolipin antibodies were confirmed; therefore, he was diagnosed with APS and treated with aspirin. If the impending CRVO is associated with visual impairment, the complication of PAMM should be considered. In the presence of retinal vasculopathy without atherosclerotic factors, APS should be considered.

An Autopsy Case of Elderly Onset Brainstem Acute Disseminated Encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM), which is a disease that causes multifocal inflammatory demyelination of the central nervous system, occurs predominantly in children and young adults. We report an autopsy case of an elderly man with brainstem ADEM that progressed over a period of about 3 months. An 82-year-old man developed disturbance of consciousness, dysphagia, and ataxic gait over a period of about 3 months. He was admitted to another hospital for aspiration pneumonia and recovered but was transferred to our hospital due to prolonged disturbance of consciousness. The patient was able to follow simple commands but had a tendency to somnolence. In addition to meningeal stimulation signs, the patient had left-dominant upper and lower limb ataxia and right-dominant limb spasticity. Brain FLAIR/T2-weighted imaging showed high-intensity lesions from the brainstem to the middle cerebellar peduncle bilaterally, medulla oblongata and upper cervical spinal cord, and T1-weighted imaging revealed contrast-enhanced lesions in the left middle cerebellar peduncle and cervical spinal cord. Although spinal fluid examination revealed elevated proteins, other laboratory tests indicated no evidence of infection, vasculitis, collagen diseases or tumors, and anti-ganglioside, anti-AQP4 and anti-MOG antibodies were negative. After admission, the patient again developed aspiration pneumonia, which progressed to acute respiratory distress syndrome, and he died on the 15th day of hospitalization. Autopsy findings indicated acute and subacute demyelination mainly in the brainstem and cerebellum, and perivascular lymphocyte and macrophage infiltration in the areas of demyelination. A postmortem diagnosis of ADEM was made based on the generally monophasic course of the disease and the absence of regenerating myelinated sheaths. There are very few reports of elderly patients with brainstem ADEM. ADEM should be considered as a differential diagnosis in patients with brainstem encephalitis.

Linear association between aging and decreased blood thiol antioxidant activity in patients with cataract.

We comprehensively assessed the roles of systemic redox markers by including both prooxidant and antioxidant markers in 121 Japanese subjects (mean ±â€…SD age, 70 ±â€…11 years; 38 men) with no ocular pathology except age-related cataract. Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured using the diacron reactive oxygen metabolite (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free-radical analyzer. Univariate analyses suggested that older age, higher pulse rate, worse best-corrected visual acuity (BCVA), higher intraocular pressure, and higher cataract grade were associated with a lower SH level. Scatterplots revealed virtually linear associations between age and the SH level (estimate, -4.4 µM/year). Multivariate analyses suggested that older age, higher systolic blood pressure, and worse BCVA were associated with a lower SH level. Neither the univariate nor multivariate analyses, except between female sex and higher dROM level, were associated with the dROM or BAP level. A lower serum SH level was the driver of aging itself and age-related decline in VA due to cataract. The serum SH level may be an excellent predictor of aging status in each subject.

A Case of Nephrotic Syndrome with Bilateral Serous Retinal Detachment and Shallow Anterior Chamber Associated with Ciliary Body Edema.

Nephrotic syndrome is a disease that causes fluid retention in the body due to loss of protein in the blood, which can lead to serous retinal detachment (SRD) in the macula. We report a case of severe SRD in both eyes and angle closure due to ciliary body edema caused by nephrotic syndrome. A 57-year-old man was admitted to the Department of Nephrology in our hospital for a thorough examination of his generalized edema. He was diagnosed with nephrotic syndrome but proved to be refractory to steroid treatment. Due to distortion symptoms in both eyes on the 30th day of hospitalization, the patient was referred to our department. Best-corrected visual acuity (BCVA) was 0.8 in the right eye and 1.0 in the left eye. Slit lamp examination and anterior segmental optical coherence tomography (OCT) showed shallow anterior chambers in both eyes. Fundus and macular OCT demonstrated severe SRD in the posterior pole of both eyes. After observing the presence of hypoalbuminemia, we considered the possibility of SRD and angle closure due to ciliary edema that resulted from the leaks associated with the nephrotic syndrome. Thereafter, ocular findings improved in conjunction with systemic symptom improvements associated with ultrafiltration and low-density lipoprotein apheresis. On the 60th day of hospitalization, his BCVA improved to 1.2 in both eyes, SRD disappeared, and the anterior chamber depth normalized. This case demonstrates the importance of recognizing SRD and angle closure associated with ciliary body edema as complications linked with nephrotic syndrome.

Comparisons between retinal vessel calibers and various optic disc morphologic parameters with different optic disc appearances: The Glaucoma Stereo Analysis Study.

The Glaucoma Stereo Analysis Study (GSAS) is a multicenter collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. This study evaluated the retinal vessel calibers and correlations using GSAS fundus photographs between retinal vessels and 38 optic nerve head (ONH) morphologic parameters comprehensively. In all 240 eyes, the mean central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were 138.4 and 216.5 µm, respectively; the CRAE correlated with age, visual field scores and 19 ONH parameters and CRVE correlated with age, intraocular pressure, visual field scores and 11 ONH parameters. Among the different optic disc appearances including focal ischemia (FI) (n = 53, 22%), generalized enlargement (GE) (n = 53, 22%), myopic glaucoma (MY) (n = 112, 47%), and senile sclerosis (SS) (n = 22, 9%), the CRAE did not differ significantly; CRVE was significantly narrower in SS than in FI and MY. In FI, GE, MY, and SS disc types, CRAE correlated with 3, 14, 9, and 2 ONH parameters, respectively, and CRVE corelated with 9, 0, 12, and 6 ONH parameters, respectively. We confirmed previous observations on the effect of retinal vessel narrowing on glaucomatous changes in the ONH and visual field. The associations between retinal vessel caliber and ONH morphologic parameters vary among different optic disc appearances, suggesting different effects of vascular changes in each disc type.

Refractive Status in Eyes Implanted with Toric and Nontoric Intraocular Lenses during Combined Cataract Surgery and Microhook Ab Interno Trabeculotomy.

PURPOSE: To compare the refractive status between eyes implanted with toric and nontoric intraocular lenses (IOLs) during combined cataract surgery and microhook ab interno trabeculotomy (µLOT), a minimally invasive glaucoma surgery (MIGS). METHODS: Twenty eyes of 20 patients who had open-angle glaucoma, cataract, and preexisting regular corneal astigmatism exceeding 1.5 diopters (D) and underwent combined µLOT and phacoemulsification were recruited retrospectively. Ten eyes were implanted with a toric IOL and 10 eyes with a nontoric IOL. The primary outcomes were the uncorrected visual acuity (UCVA) and refractive cylinder at 3 months postoperatively. RESULTS: The mean UCVA of the toric IOL group (logarithm of the minimum angle of resolution (logMAR), 0.23 ± 0.25) was significantly better than that of the nontoric IOL group (logMAR, 0.45 ± 0.26) at 3 months postoperatively (p < 0.05). The mean absolute residual refractive cylinder of the nontoric IOL group (2.25 ± 0.62 D) was significantly greater than that of the toric IOL group (1.30 ± 0.68 D) (p < 0.05). Postoperatively, 60% of eyes in the toric IOL group and 10% in the nontoric IOL group had an absolute refractive astigmatism level of 1.5 D or less. Surgically induced astigmatism (0.77 ± 0.43 D for toric group and 0.60 ± 0.32 D for nontoric group) and IOP reduction (33.9 ± 15.6% for toric group and 29.4 ± 11.7% for nontoric group) were not different between groups. CONCLUSIONS: Use of toric IOL during combined cataract surgery and µLOT is possible and better than not, but physician should prevent their patient of persisting residual astigmatism. The study was registered at https://www.umin.ac.jp/, and the clinical trial accession number is https://clinicaltrials.gov/ct2/show/UMIN000043141.

Saccharopinuria accompanied by hyperammonemia and hypercitrullinemia presented with elderly-onset epilepsy, progressive cognitive decline, and gait ataxia.

We report a case of saccharopinuria with hyperammonemia and hypercitrullinemia in a Japanese woman who presented with elderly-onset epilepsy, progressive cognitive decline, and gait ataxia. Blood amino acid analysis revealed an increase in citrulline, cystine, and lysine levels, and urine amino acid analysis showed increased citrulline and cystine levels. Urine metabolomics revealed an increased saccharopine level, leading to the definitive diagnosis of saccharopinuria. In western blots of liver biopsy samples, normal citrin levels were observed, suggesting that adult-onset citrullinemia type 2 (CTLN2) was not present. In addition, decreased argininosuccinate synthetase (ASS) levels were observed, and ASS1 gene, a causative gene for citrullinemia type 1 (CTLN1), was analyzed, but no gene mutations were found. Because the causes of hypercitrullinemia were not clear, it might be secondary to saccharopinuria. Muscle biopsy findings of the biceps brachii revealed diminished cytochrome c oxidase (COX) activity, mitochondrial abnormalities on electron microscopy and p62- positive structures in immunohistochemical analyses. Saccharopinuria is generally considered a benign metabolic variant, but our case showed elevated lysine and saccharopine levels causing ornithine circuit damage, mitochondrial dysfunction, and autophagy disorders. This may lead to so far unknown neurological disorders.

Sympathetic ophthalmia after 27-G pars plana vitrectomy.

BACKGROUND: Sympathetic ophthalmia (SO) is a bilateral diffuse uveitis that can arise after ocular trauma or ocular surgery in the inciting eye. Pars plana vitrectomy (PPV) is one of the risk factors for SO. Several reports have described SO developing after 23- and 25-G PPV, but none have described SO occurring after 27-G PPV. We describe herein a case of SO after 27-G PPV for rhegmatogenous retinal detachment. CASE PRESENTATION: A 42-year-old woman presented with visual disturbance in the right eye. Best-corrected visual acuity (BCVA) was 6/200 in the right eye. Fundus examination revealed off-macula retinal detachment with retinal tears at both ends of retinal lattice degeneration at the temporal-oven peripheral retina of the right eye. We therefore performed 27-G sutureless PPV on the right eye. After 12 days, the retina was reattached, and BCVA improved to 6/30 in the right eye. Fifteen days postoperatively, she experienced headache and reduced vision in both eyes. Symptoms gradually worsened, and she visited our hospital 21 days postoperatively. BCVA was 6/30 in the right eye and 6/15 in the left eye. Slit-lamp examination revealed uveitis in the anterior chambers of both eyes, and fundus examination showed papillitis and subretinal detachment at the posterior poles of both eyes. Optical coherence tomography revealed subretinal fluid in the maculae of both eyes and fluorescein angiography showed multiple hyperfluorescent leakage sites in the retinal pigment epithelium. Cerebrospinal fluid examination showed pleocytosis and human leukocyte antigen testing showed expression of the DR04 phenotype; therefore, the patient was diagnosed with SO. She was treated with steroid therapy, and her visual disturbance subsided and the subretinal fluid improved as well. Her BCVA was 6/15 for the right eye and 6/5 for the left eye 93 days after the initial surgery. CONCLUSION: The present case shows that even if the sclerotomy site of 27-G PPV is small, there is still a risk of SO occurring in the eyes of patients who underwent transconjunctival vitrectomy. Ophthalmologists should recognize SO as complication of 27-G PPV and carry out proper management as early as possible.

Intraobserver and interobserver agreement among anterior chamber angle evaluations using automated 360-degree gonio-photos.

PURPOSE: To investigate the reproducibility for the iridocorneal angle evaluations using the pictures obtained by a gonioscopic camera, Gonioscope GS-1 (Nidek Co., Gamagori, Japan). METHODS: The pragmatic within-patient comparative diagnostic evaluations for 140 GS-1 gonio-images obtained from 35 eyes of 35 patients at four ocular sectors (superior, temporal, inferior, and nasal angles) were conducted by five independent ophthalmologists including three glaucoma specialists in a masked fashion twice, 1 week apart. We undertook the observer agreement and correlation analyses of Scheie's angle width and pigmentation gradings and detection of peripheral anterior synechia and Sampaolesi line. RESULTS: The respective Fleiss' kappa values for the four elements between manual gonioscopy and automated gonioscope by the glaucoma specialist were 0.22, 0.40, 0.32 and 0.58. Additionally, the respective intraobserver agreements for the four elements by the glaucoma specialist each were 0.32 to 0.65, 0.24 to 0.71, 0.35 to 0.70, and 0.20 to 0.76; the Fleiss' kappa coefficients for the four elements among the three glaucoma specialists were, respectively, 0.31, 0.38, 0.31, and 0.17; the Fleiss' kappa coefficients for the angle width and pigmentation gradings between the two glaucoma specialists each were 0.30 to 0.35, and 0.29 to 0.43, respectively. Overall, the Kendall's tau coefficients for the angle gradings reflected the positive correlations in the evaluations. CONCLUSION: Our findings suggested slight-to-substantial intraobserver agreement and slight-to-fair (among the three) or fair-to-moderate (between the two each) interobserver agreement for the angle assessments using GS-1 gonio-photos even by glaucoma specialists. Sufficient training and a solid consensus should allow us to perform more reliable angle assessments using gonio-photos with high reproducibility.

Effect of Toric Intraocular Lens Implantation on Visual Acuity and Astigmatism Status in Eyes Treated With Microhook Ab Interno Trabeculotomy.

PRCIS: Use of toric intraocular lenses is a reasonable option for better visual outcomes when a combined minimally invasive glaucoma surgery (MIGS) and cataract surgery is performed in eyes with corneal astigmatism. PURPOSE: To assess the efficacy of toric intraocular lenses (IOLs) in combined cataract and MIGS, visual and refractive outcomes were compared between eyes implanted with nontoric and toric IOLs during microhook ab interno trabeculotomy triple procedures. METHODS: Glaucomatous eyes with preexisting corneal astigmatism exceeding -1.5 D implanted with nontoric (n=10) or toric (n=10) IOLs were evaluated retrospectively. The uncorrected visual acuity (UCVA) and refractive astigmatism preoperatively and 3 months postoperatively were compared. RESULTS: Preoperatively, the groups had similar logarithm of the minimum angle of resolution (logMAR) UCVAs and refractive astigmatism. Postoperatively, the logMAR UCVA (toric, 0.07±0.07; nontoric, 0.33±0.30; P=0.0020) was significantly better and the refractive astigmatism (toric, -0.63±0.56 D; nontoric, -1.53±0.74 D; P=0.0110) significantly less in the toric group. The toric group had postoperative improvements in the logMAR UCVA (-0.58, P=0.0039) and refractive astigmatism (+1.45 D, P=0.0195). Vector analyses showed the postoperative centroid magnitude of refractive astigmatism was less in the toric group (0.23 D at 83 degrees) than the nontoric group (1.03 D at 178 degrees). Postoperatively, 70% of eyes in the toric group had 1.0 D or less refractive astigmatism compared with 10% in the nontoric group. Surgically induced astigmatism (nontoric group, 0.62 D at 10 degrees; toric group, 0.50 D at 113 degrees) and intraocular pressure reduction (22% in both groups) did not differ between groups. CONCLUSIONS: Better visual outcomes may be achieved with toric IOLs when a combined MIGS/cataract surgery is performed in eyes with corneal astigmatism.

Efficacy and Safety of Intravitreal Aflibercept Injection in Japanese Patients with Neovascular Glaucoma: Outcomes from the VENERA Study.

INTRODUCTION: Neovascular glaucoma is characterized by neovascularization of the iris and anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may decrease intraocular pressure (IOP) and improve neovascularization. The VENERA study assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma. METHODS: This was a 5-week, single-arm, nonrandomized, open-label, phase 3 study performed at 7 study sites in Japan that enrolled Japanese patients with anterior segment neovascularization and IOP > 25 mmHg who had not undergone (within 30 days prior), nor were imminently scheduled to undergo (within 8 days following) intraocular surgeries, including panretinal photocoagulation (PRP). Patients received background therapy plus 2 mg IVT-AFL at baseline. Background therapy with systemic IOP-lowering drugs was prohibited for 3 days before day 1 and until IOP evaluation at week 1. The primary endpoint was the change in IOP from baseline to week 1 and the secondary endpoint was the proportion of patients with an improvement of ≥ 1 grade of neovascularization of the angle (NVA) from baseline to week 1. RESULTS: Sixteen patients received treatment (full analysis set); the per-protocol set comprised 15 patients. The mean IOP decreased from 34.1 mmHg at baseline to 25.8 mmHg at week 1 (mean change, -8.3 mmHg [95% confidence interval; CI -12.2 to -4.4; P = 0.0004]). At week 1, 81.3% of patients had an improvement in the grade of neovascularization of the iris (NVI) and 50.0% of patients had an improvement in NVA grade. The proportion of patients with controlled IOP (≤ 21 mmHg) was 43.8% (95% CI 19.8-70.1) at week 1, and increased to 56.3% at week 2 and 86.7% at week 5. The most common ocular treatment-emergent adverse event was eye pain, which occurred in 4 patients (25.0%). CONCLUSIONS: IVT-AFL was associated with statistically significant and clinically meaningful IOP reductions, without concomitant use of systemic IOP-lowering drugs or PRP. The safety profile was consistent with the known safety profile of IVT-AFL. These findings supplement those from the previous VEGA study, and suggest that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03639675.

Evaluation of Redox Profiles of the Serum and Aqueous Humor in Patients with Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH.