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We investigated the effects of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammatory gene expression in immortalized ARPE-19, and primary human and mouse retinal pigment epithelial (RPE) cells. Sulfane sulfur molecules were significantly increased in GSSSG-treated ARPE-19 cells. GSSSG prevented the LPS-induced upregulation of interleukin (IL)-1β, IL-6, and C-C motif chemokine ligand 2 (CCL2) in ARPE-19/primary RPE cells. Moreover, GSSSG prevented the activation of the nuclear factor-kappa B p65 subunit, and promoted the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in LPS-treated ARPE-19 cells. ERK1/2 inhibition prevented the GSSSG-mediated inhibition of LPS-induced IL-6 and CCL2 upregulation. Additionally, ERK1/2 activation prevented the upregulation of these genes in the absence of GSSSG. Knockdown of HMOX1 or NRF2, known as anti-oxidative genes, did not affect the activity of GSSSG in the context of LPS stimulation. These findings suggest that GSSSG attenuates LPS-induced inflammatory gene expression via ERK signaling hyperactivation, independently of the NRF2/HMOX1 pathway.

Calpain activation induces retinal ganglion cell (RGC) death, while calpain inhibition suppresses RGC death, in animal studies. However, the role of calpain in human retinal disease is unclear. This study investigated a new strategy to study the role of calpain based on real-time imaging. We synthesized a novel fluorescent probe for calpain, acetyl-l-leucyl-l-methionine-hydroxymethyl rhodamine green (Ac-LM-HMRG) and used it for real-time imaging of calpain activation. The toxicity of Ac-LM-HMRG was evaluated with a lactate dehydrogenase cytotoxicity assay, retinal sections, and electroretinograms. Here, we performed real-time imaging of calpain activation in a rat model. First, we administered N-methyl-d-aspartate (NMDA) to induce retinal injury. Twenty minutes later, we administered an intravitreal injection of Ac-LM-HMRG. Real-time imaging was then completed with a noninvasive confocal scanning laser ophthalmoscope. The inhibitory effect of SNJ-1945 against calpain activation was also examined with the same real-time imaging method. Ac-LM-HMRG had no toxic effects. The number of Ac-LM-HMRG-positive cells in real-time imaging significantly increased after NMDA injury, and SNJ-1945 significantly lowered the number of Ac-LM-HMRG-positive cells. Real-time imaging with Ac-LM-HMRG was able to quickly quantify the NMDA-induced activation of calpain and the inhibitory effect of SNJ-1945. This technique, used as a companion diagnostic system, may aid research into the development of new neuroprotective therapies.

Malignant hypertension, a form of hypertensive emergency, causes acute damage in vital organs such as the brain, eyes, and kidneys. We aimed to examine the concurrency of acute hypertensive damage across the target organs to elucidate the underlying analogous pathophysiology. This single-center retrospective study evaluated the characteristics of organ damage, short-term clinical course, and interorgan relationships in patients with malignant hypertension treated between 2008 and 2019. Baseline characteristics of 20 patients who met our inclusion criteria were mean age 48 ± 13 years and blood pressure 222 ± 18/142 ± 16 mmHg; the median estimated glomerular filtration rate and urinary protein level were 49 mL/min/1.73 m2 (interquartile range [IQR] 27–79) and 1.9 g/g creatinine (IQR 0.2–4.0), respectively. Posterior reversible encephalopathy syndrome (PRES) was found in 60% of patients with major involvement and a wide variety of distribution patterns in the brainstem. In the fundus, serous retinal detachment was found in 60% of patients. Patients with PRES and serous retinal detachment showed higher levels of urinary protein than those without symptoms (P = 0.007 and 0.02, respectively), and proteinuria >1 g/g creatinine highly complicated both PRES and serous retinal detachment (91%). Matrix analysis also showed that the three symptoms were highly associated with each other. These results demonstrate the close relationship and concurrency of hypertensive acute organ damage in the brain, eyes, and kidneys. A common analogous mechanism, such as hyperperfusion-induced capillary leakage in each organ, implies an underlying pathophysiology of PRES, serous retinal detachment, and proteinuria.

The success of surgical treatment for idiopathic epiretinal membrane (ERM) is measured by postoperative best-corrected visual acuity (BCVA), metamorphopsia, and foveal retinal sensitivity (RS).This study searched for predictive biomarkers of surgical success by determining the association between foveal RS and various aspects of vessel density (VD) in the fovea of patients with ERM. The study examined 25 eyes of 25 patients with ERM who underwent 27-gauge microincision vitrectomy surgery (MIVS). RS was measured with microperimetry (MP-3; NIDEK) at four central points in the fovea with an interpoint distance of 2°. VD was measured with SD-OCT (RS 3000; NIDEK) within the 1-mm2 square defined by the 4 RS points at various depths, including the superficial and deep retinal capillary plexus (SCP and DCP, respectively). Though VD did not change throughout the follow-up period, BCVA and RS significantly improved 1 and 3 months after surgery, respectively (both P

To investigate the effect of blood flow in the temporal optic nerve head (ONH) and peripapillary chorioretinal atrophy (PPA) zone on central visual field (VF) defects and progression in eyes with open-angle glaucoma (OAG) and myopic disc.Retrospective longitudinal medical chart review.This study comprised 366 eyes of 245 OAG patients with myopic disc, followed for at least 2 years with at least 5 reliable VF tests. OCT and laser speckle flowgraphy (LSFG) were performed at baseline.We analyzed the relationship between temporal ONH-tissue mean blur rate (MBR), temporal PPA-tissue MBR, total deviation (TD)-central, and TD-central slope with a linear mixed-effects model. Additionally, we investigated background factors influencing temporal PPA-tissue MBR. Main outcome measures were basic ophthalmic and systemic variables, baseline ONH-tissue MBR, baseline PPA-tissue MBR, baseline TD, and TD slope.Lower temporal ONH-tissue MBR was associated with both worse TD-central and faster TD-central slope (β = 0.30, P0.001; β = 0.18, P = 0.001, respectively). However, lower temporal PPA-tissue MBR was only associated with faster TD-central slope (β = 0.15, P = 0.005). Lower ONH-tissue MBR and lower PPA-tissue MBR were significant independent contributors to worse TD-central slope, after adjusting for potential confounding factors (β = 0.12 to 0.15, P0.05). The multivariate analysis showed that lower pulse rate, larger temporal PPA area, and lower circumpapillary retinal nerve fiber layer thickness were associated with lower PPA-tissue MBR (P0.05).Measurement of systemic variables and LSFG analysis might help clinicians to predict central VF defect severity and progression in OAG eyes with myopic disc.

To screen for the 328 bp Alu insertion (c.4052_4053ins328, p.Tyr1352Alafs) in RP1 in a group of retinitis pigmentosa (RP) patients who had been previously identified with a heterozygous deleterious mutation in the gene. Prospective, clinical and experimental study. The Alu insertion in RP1 was screened with an optimized PCR-based method in 26 RP patients with a heterozygous deleterious mutation (nonsense or frameshift) in RP1 that had been identified in a preceding genetic study. The genetic location of the previously identified mutation and its inheritance pattern were assessed. Out of 26 RP patients with a heterozygous deleterious mutation in RP1, 5 (19.2%) were found to carry an additional heterozygous Alu insertion, presumably resulting in a compound heterozygous state. This included 3 patients who had been previously diagnosed as autosomal dominant RP based on genetic findings. They were re-diagnosed as having an autosomal recessive disease following our new findings. In all patients identified with the Alu insertion, the other mutations found in the preceding study were outside the defined region in exon 4 (encoding amino acids 677 to 917) in which truncation mutations have been suggested to exert a dominant negative effect. The founder Alu insertion in RP1 is an important cause of autosomal recessive RP in Japanese patients and can be missed in standard targeted resequencing. Screening optimized for this mutation is warranted, particularly in patients with a heterozygous deleterious mutation outside the defined region in exon 4 of RP1.

To report a unique case of nivolumab-induced uveitis and the results of a cytokine analysis of an intraocular fluid sample.A 61-year-old male patient undergoing treatment for renal cell carcinoma with nivolumab presented with bilateral uveitis. Severe anterior uveitis and vitreous opacity coincided with decreased visual acuity only in his left eye. Iris damage was present in this eye because of previous complicated cataract surgery. Vitrectomy was performed to remove the vitreous opacity, and visual acuity recovered postoperatively. A cytokine analysis of an intraocular fluid sample revealed a high level of interleukin-6, granulocyte-colony stimulating factor and interferon-inducible protein-10.This case indicates that nivolumab-induced uveitis might be more severe in eyes with a damaged iris, and that vitrectomy should be effective for vitreous opacity. A cytokine analysis of the ocular fluid indicated that multiple types of cell might be related to the inflammation process.

The genetic basis of Japanese autosomal recessive retinitis pigmentosa (ARRP) remains largely unknown. Herein, we applied a 2-step genome-wide association study (GWAS) in 640 Japanese patients. Meta-GWAS identified three independent peaks at P A, p.G843E) of unknown significance. mRNA harboring c.2528 G > A failed to restore rhodopsin mislocalization induced by morpholino-mediated knockdown of eys in zebrafish, consistent with the variant being pathogenic. c.2528 G > A solved an additional 7.0% of Japanese ARRP cases. The third peak was in linkage disequilibrium with a common non-synonymous variant (c.7666 A > T, p.S2556C), possibly representing an unreported disease-susceptibility signal. GWAS successfully unraveled genetic causes of a rare monogenic disorder and identified a high frequency variant potentially linked to development of local genome therapeutics., Koji Nishiguchi et al. identify three genetic variants within the EYS gene that are associated with retinitis pigmentosa using a genome-wide association study. They demonstrate that one of these variants (G843E) causes retinal dysfunction in zebrafish, suggesting a causal role for EYS in retinitis pigmentosa.

PURPOSE To evaluate retinal vessel density and retinal sensitivity (RS) after macular hole surgery with the superior inverted internal limiting membrane flap technique. METHODS Retrospective, observational case series. Twenty-one patients with idiopathic macular hole underwent 27-gauge vitrectomy with the superior inverted internal limiting membrane flap technique and triamcinolone acetonide. Measurements included RS, which was measured with microperimetry, as well as retinal vessel density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), which was measured with optical coherence tomography angiography. All parameters were evaluated in the superior and inferior sectors of the macula preoperatively and 1, 3, and 6 months postoperatively. RESULTS Six months postoperatively, retinal thickness in the inferior sector was unchanged, but retinal thickness in the superior sector decreased significantly (P < 0.01). SCP vessel density in both sectors was unchanged at all postoperative time points. DCP vessel density in both sectors increased very significantly at 3 months (P < 0.01) and returned to baseline at 6 months. RS in the inferior sector increased by 47% 3 months postoperatively and by 61% 6 months postoperatively (P < 0.05 and P < 0.001, respectively), but RS in the superior sector increased only at 6 months postoperatively and only by 22% (P < 0.05). CONCLUSION Lower recovery of RS in the superior sector suggests that internal limiting membrane peeling might affect the postoperative visual function.

Rhegmatogenous retinal detachment (RRD) is a serious condition that can cause blindness without surgical treatment. RRD occurs when a retinal tear or hole allows fluid to accumulate below the retinal surface, causing the retina to separate from the underlying layers. RRD is difficult to treat because each case is unique, varying with the location, size, and duration of the detachment, as well as patient age. The first successful methods to reattach the retina in RRD used thermocautery to repair the detachment. Many renowned ophthalmologists continued to study RRD and developed many new surgical approaches, notably: scleral buckling (SB), in which a silicone band is placed around the eye to reduce traction on the retina caused by the vitreous humor that fills the eye; pars plana vitrectomy (PPV), which eliminates traction on the retina by removing the vitreous; and pneumatic retinopexy (PR), in which the retina is reattached by pushing it back into place with an expanding gas bubble injected into the eye. However, no consensus has been reached on which approach is ideal. Furthermore, recent surgical and non-surgical breakthroughs, such as artificial vitreous substitutes and neuroprotective drugs, must also be considered. Thus, this review provides a guide for ocular specialists and non-specialists on the historical background of RRD, summarizes the three current main techniques (SB, PR and PPV) compares these three techniques, and provides an overview of new technologies that promise to greatly improve outcomes after RRD surgery.

This study searched for early predictive vascular biomarkers for visual outcomes in eyes with macular edema caused by branch retinal vein occlusion (BRVOME). Twenty-four eyes of 24 subjects with BRVOME were treated with the intravitreal injection of ranibizumab (IVR) for at least 6 months. We measured mean blur rate (MBR) in the optic nerve head (ONH) and vessel density (VD) in the macula with laser speckle flowgraphy and optical coherence tomography angiography, respectively. Six-month post-IVR best-corrected visual acuity (BCVA) was correlated positively with age, pre-IVR BCVA, 1-month post-IVR BCVA, 3-month post-IVR BCVA and pre-IVR systolic blood pressure (P

PURPOSE To compare glaucoma severity with ocular microcirculation, measured with either laser speckle flowgraphy (LSFG) or optical coherence tomography angiography (OCTA). METHODS We retrospectively studied 82 eyes of 82 open-angle glaucoma (OAG) patients who underwent same-day LSFG and OCTA examinations, with 20 eyes of 20 healthy subjects as controls. In OCTA images, vessel density (VD) (%) was calculated in concentric regions (regions 1, 2 and 3: R1, R2 and R3, respectively) defined by 1.6-, 3.2- and 3.6-mm-diameter circles around the optic nerve head (ONH). In R3, the large vessels were automatically masked to calculate pure capillary density (auto R3 VD). LSFG-measured mean blur rate (MBR) was examined in the overall ONH (MA), vessel-area ONH (MV) and tissue-area ONH (MT). RESULTS Auto R3 VD had high reproducibility (coefficient of variation: 1.65-3.88%) and accurately reflected manual R3 VD [mean bias: -0.0087% (auto R3 VD - manual R3 VD)]. MA and MT decreased significantly with OAG severity, especially in the early OAG stages (control vs. mild: p = 0.003 and p

The purpose of the study is to investigate the correlation between intraocular anti-retinal antibodies and clinical measurements in patients with rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinopathy (PVR).Aqueous humor and vitreous samples were collected from patients with RRD, PVR, and from control subjects with macular hole. The levels of total protein (TP), IgG, and anti-retinal antibodies were determined with a bicinchoninic acid assay, enzyme-linked immunosorbent assay, and dot blot, respectively. Correlations between these measurements were assessed using Pearson's correlation test. Analysis of variance followed by a post-hoc test or the Student t-test was used to compare differences between groups.The levels of anti-retinal antibodies and IgG were correlated with each other (P 0.010). The IgG concentration was higher in patients with PVR than in controls in both the aqueous humor (P 0.001) and the vitreous (P 0.001), but not in patients with RRD. Conversely, TP levels and anti-retinal antibodies in both ocular fluids from RRD and PVR patients did not significantly differ from the controls. In a subgroup analysis, vitreal anti-retinal antibody levels were correlated with average macular thickness in the re-attached macula following surgery for macula-off RRD/PVR (P = 0.012). Furthermore, patients with post-operative cystoid macular edema had a higher level of vitreal anti-retinal antibodies than those without (P = 0.009).Intravitreal anti-retinal antibodies were increased in the eyes with maculopathy after surgical intervention for RRD/PVR.

Systemic oxidative stress is thought to be an important factor in the pathogenesis of glaucoma. In particular, low systemic antioxidative capacity, which normally counters oxidative stress, may contribute to glaucoma. Thus, we investigated the association between biological antioxidant potential (BAP), a biomarker of systemic antioxidative capacity, and glaucoma severity in patients with open-angle glaucoma (OAG). This study included 480 eyes of 240 patients with OAG and 66 healthy control eyes. We measured the BAP serum level with a free radical analyzer and compared it with a weighted estimate of the number of retinal ganglion cells (wrgc), derived from circumpapillary retinal nerve fiber layer thickness and visual field mean deviation. We found that wrgc was uncorrelated with BAP in the overall, male, and female OAG patients, but was correlated in young (aged ≤ 65 years) male OAG patients (better eye: r = 0.33, P = 0.02; worse eye: r = 0.27, P = 0.047). Furthermore, a mixed-effects regression analysis revealed that BAP was an independent contributing factor to wrgc in young male OAG patients (P = 0.02). Thus, systemic antioxidant capacity was associated with glaucomatous damage in relatively young male patients, suggesting that anti-oxidant therapy might be more effective in these patients.

The purpose of this study was to investigate the relationship between laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA) measurements of ocular microcirculation in normal and open-angle glaucoma (OAG) subjects. This study included 18 eyes of 18 OAG patients and ten eyes of ten age-matched healthy controls. LSFG was used to measure mean blur rate (MBR) in the optic nerve head (ONH) vessel area (MV) and tissue area (MT). OCTA was used to measure a new parameter, peripapillary relative intensity (PRI), in the superficial retina, superficial choroid, and deep choroid. Statistical associations were then determined. MV, MT, superficial-retinal PRI, and superficial-choroidal PRI were lower in the OAG subjects than the controls (P = 0.02, P

To report a case of endophthalmitis associated with Purpureocillium lilacinum (P. lilacinum) during infliximab treatment for surgically induced necrotizing scleritis, successfully treated with 27-gauge vitrectomy. A single case report. A 71-year-old man who had undergone immunosuppressive therapy, including infliximab, for surgically induced necrotizing scleritis (SINS) in his left eye complained of visual disturbance and eye pain in the eye. He had a past history of surgery for recurrent pterygium: pterygium excision, amnion transplantation with mitomycin C and limbal transplantation. Visual acuity in the left eye was counting fingers at 30 cm, and intraocular pressure was 3.0 mmHg. Slit-lamp examination revealed the presence of anterior chamber cells (3+), and a B-mode ultrasound scan showed a vitreous opacity. We made a diagnosis of endophthalmitis and performed 27-gauge microincision vitrectomy surgery (27GMIVS) with antibiotic perfusion of ceftazidime, vancomycin and voriconazole. Intraoperative findings included a fungus-like ball-shaped opacity in the vitreous, and a close-to-normal retinal appearance. A vitreous body culture identified the presence of P. lilacinum. After 2 months of antibacterial and antifungal therapy, inflammation decreased and visual acuity recovered to 20/100. This is the first report of a case of endophthalmitis associated with P. lilacinum during infliximab treatment for SINS. Scleral thinning due to necrotizing scleritis, especially during immunosuppressive therapy, is a risk factor for endophthalmitis. We found that 27GMIVS was a useful strategy for such a challenging clinical situation.

Purpose To screen for anti-recoverin antibodies in elderly patients with retinitis pigmentosa (RP) with or without cancer and cross-sectionally characterize the seropositive patients clinically. Methods Serum from 75 RP patients who had been tested for mutations in a panel of 83 RP genes and 73 normal controls, all aged 50-80 years, were screened for anti-recoverin antibodies by Western blot using recombinant recoverin, retinal lysate from a marmoset and commercial anti-recoverin antibodies as a control. Results Three RP patients with typical pigmentary degeneration of the 75 (4.0%) were seropositive for anti-recoverin antibody. Pathogenic mutations were identified in two seropositive RP patients. All three patients had visual impairment since childhood and were diagnosed as RP by the age of 30. The severity of the retinopathy varied greatly among these three patients, ranging in visual acuity from light perception OU to 20/30 OU. Retinitis pigmentosa (RP) patients with a history of cancer were more likely to have anti-recoverin antibodies (3/14; 21.4%) than those without (0/61; 0%; p = 0.005, Fischer exact test). All 73 healthy controls with no history of cancer were also seronegative. Conclusion Our results show that serum anti-recoverin antibodies can be detected in typical RP patients with identified pathogenic mutations and that a history of cancer may increase the risk of developing anti-recoverin antibodies.

PURPOSE To investigate the effect of optic nerve head (ONH) tissue vasoreactivity on glaucoma visual field defect progression. METHODS This prospective, longitudinal study comprised 28 eyes of 16 patients with open-angle glaucoma. Baseline data were obtained from oxygen inhalation testing, including laser speckle flowgraphy measurements of tissue-area mean blur rate (MT), which represents ONH tissue blood flow, and the mean percentage change in MT (MT-change). Follow-up data were collected for at least 2 years, including at least 5 reliable visual field tests. The average total deviation (TD) was calculated in each sector of the Garway-Heath map; in this study, superior, central and inferior TD corresponded to inferior, temporal and superior MT or MT-change, respectively. MT and MT-change in three sectors per eye were included as explanatory variables in a multivariable linear mixed-effects model, with TD slope set as the response variable. RESULTS At baseline, lower MT and higher diastolic blood pressure were associated with lower MT-change (p

Retinal detachment due to giant retinal tears (GRTs), tears larger than 90°, is rare and difficult to treat. Here, we show and compare surgical results of 23-, 25- and 27-gauge (G) micro-incision vitrectomy surgery (MIVS) for GRT. Retrospective and interventional case series. Retrospective review of 41 eyes of 38 patients with GRT who underwent MIVS. Surgical outcomes after MIVS, including reattachment rates and postoperative complications, were compared between instrument gauges. All patients were followed for at least 6 months postoperatively. MIVS with 23G, 25G and 27G instruments was performed in 7, 19 and 15 eyes, respectively. Silicone oil (SO) was used in 34 of 41 eyes (83%) with a mean removal time of 43.8 days after first surgery. Best-corrected visual acuity (BCVA) was recovered or maintained in 39 eyes (95%). Reattachment was attained after initial surgery in 38 of 41 eyes (93%) (23G: 6/7 [86%]; 25G: 17/19 [89%]; 27G: 15/15 [100%]). Final reattachment was eventually achieved in all eyes (two eyes needed support from scleral encircling). Postoperative complications occurred in 16 eyes (39%) (23G: 3/7 [43%]; 25G: 8/19 [42%]; 27G: 5/15 [33%]), including macular pucker, cystoid macular edema, macular hole, subretinal perfluorocarbon liquid, retinal folds, vitreous hemorrhage and redetachment. There were no significant differences between the three groups in rate of high myopia, GRT size, operation time, phacovitrectomy rate, SO usage rate, initial reattachment rate, final reattachment rate, preoperative BCVA, final BCVA or rate of postoperative complications. Despite occasional postoperative complications, primary MIVS, regardless of gauge size, appears to be a safe and feasible option for GRT surgery.

Aims Evaluation of the retinal microcirculation is key to understanding retinal vasculopathies, such as diabetic retinopathy. Laser speckle flowgraphy (LSFG) has recently enabled us to directly evaluate the vascular resistance in both retinal vessels and capillaries, non-invasively. We therefore assessed whether retinal vessel blood flow and/or the capillary microcirculation are associated with blood flow in the cervical arteries in diabetic patients without severe retinopathy. Methods We enrolled 110 type 2 diabetes patients, with no or mild non-proliferative diabetic retinopathy, in this prospective cross-sectional study. We measured the resistivity indices (RIs) of the retinal vessel and capillaries by LSFG and those of cervical arteries by Doppler ultrasonography, followed by analyzing associations. Results The RIs of not only the carotid but also vertebral arteries were associated with those of retinal vessel blood flow and the retinal capillary microcirculation. Multiple regression analyses revealed these associations to be independent of other explanatory variables including age and diabetes duration. Conclusions We obtained novel and direct evidence demonstrating a close association between the retinal microcirculation and cervical artery hemodynamics in diabetic patients. These findings suggest shared mechanisms to underlie micro- and macro-angiopathies. Thus, high vascular resistance of cervical arteries may be a risk of developing retinopathy.

Background Group B streptococcus (GBS), a gram-positive coccus that occasionally causes neonatal sepsis or invasive infection in the elderly, has been considered a rare cause of endogenous bacterial endophthalmitis (EBE). However, the number of invasive GBS infections is increasing, particularly in elderly patients with underlying conditions such as diabetes mellitus (DM), cardiovascular disease and cancer. We report 6 cases of EBE caused by GBS and review the literature. Methods Retrospective case series and literature review. Results In the current case series, 6 eyes of 6 patients developed EBE caused by GBS. The average age was 73.5 years. The focus of infection included the urinary tract, cellulitis, arthritis, peritonitis, catheter-associated infection and endocarditis. Four patients had DM. While all 6 strains were sensitive to β-lactams (penicillins and cephems), 4 strains were resistant to levofloxacin (no data for 1 isolate). Each case was treated with the systemic antibiotic to which the individual strain was sensitive. All cases showed poor visual acuity at presentation (decimal visual acuity: less than 0.03). Vitrectomy with intravitreal antibiotics injection was performed in 4 cases. Visual acuity recovered in 4 cases and did not recover in 2 cases, even after vitrectomy. The literature review of 53 eyes of 41 patients revealed that 60% of eyes finally lost all vision, and death occurred in 2 cases. Initial visual acuity of less than counting fingers was associated with a final outcome of lost vision. Of 41 patients, 13 (32%) had DM as an underlying medical condition. The most common extra-ocular infection focus was endocarditis (37%). Conclusions DM is common in patients with EBE caused by GBS. While the 4 cases in the current report had a relatively good visual acuity outcome, despite poor initial visual acuity, the literature review indicated that EBE caused by GBS is generally a severe condition with a poor prognosis. The current study also indicates the importance of considering the possibility of endocarditis on encountering EBE caused by GBS.

This study evaluated age-related changes in the superficial and deep retinal capillary plexus (SCP and DCP, respectively) and in the foveal avascular zone (FAZ). SCP and DCP perfusion density (PD) were measured in optical coherence tomography angiography (OCTA) macular scans of 145 eyes of 145 healthy Japanese subjects, and findings were compared with SCP FAZ and clinical data. We found that age was negatively correlated with SCP and DCP PD (r = −0.17, P = 0.04 and r = −0.20, P = 0.02, respectively) and positively correlated with FAZ area (r = 0.18, P = 0.03). SCP and DCP PD were correlated with each other (r = 0.67, P P = 0.03; r = −0.25, P P P = 0.01 and P < 0.001, respectively) in women than men. SCP and DCP PD were positively correlated with estimated glomerular filtration rate (r = 0.17, P = 0.03 and r = 0.24, P P = 0.02 and P P

Purpose: To compare optic nerve head (ONH) blood flow in healthy eyes, eyes with preperimetric glaucoma (PPG), and eyes with mild normal-tension glaucoma (NTG) using laser speckle flowgraphy (LSFG).Methods: In 172 eyes (normal: 44 eyes; PPG: 62 eyes; mild NTG: 66 eyes), LSFG was used to measure mean blur rate in the ONH tissue area (MBRT), an index of capillary blood flow. Multiple regression analysis was performed to determine factors affecting circumpapillary retinal nerve fiber layer thickness (cpRNFLT), mean deviation (MD) and pattern standard deviation (PSD) of the visual field.Results: Despite similar characteristics in age, refractive error and systemic variables among the study groups, MBRT in the normal eyes differed significantly from both the PPG and mild NTG eyes (P = 0.001, P < 0.001, respectively). Multiple regression analysis revealed that MBRT was an independent factor affecting cpRNFLT, MD and PSD (P < 0.001, P = 0.001, P = 0.003, respectively).Conclusion: ONH blood flow was detec...

To present phenotypic features of 22 patients with S-antigen (SAG) mutations.Retrospective cohort study.Twenty-one Japanese patients from 16 families with a homozygous c.924delA mutation and 1 patient with a homozygous c.636delT mutation in the SAG gene.Clinical records on symptoms; best-corrected visual acuity; and Goldmann perimetry, fundus photography, fundus autofluorescence (FAF), OCT, and electroretinography results were reviewed.Best-corrected visual acuity, Goldmann perimetry results, imaging findings, and electroretinography results.Ten patients had Oguchi disease and 12 had retinitis pigmentosa (RP) with mean follow-up periods of 13.8 and 10.2 years, respectively. Retinitis pigmentosa patients were older (mean age, 56.0 years) than those with Oguchi disease (mean age, 22.1 years; P0.001) at the initial visit. Night blindness noted in childhood was the most common initial symptom for both Oguchi disease (80.0%) and RP (91.7%) patients. Best-corrected visual acuity in the logarithm of the minimum angle of resolution (logMAR) was well preserved in Oguchi disease patients (mean, 0.02 logMAR in both eyes) but reduced in most RP patients (mean, 1.32 logMAR [right eye] and 1.35 logMAR [left eye]). Similarly, the visual field in the retinal area was preserved in Oguchi disease patients (mean, 677 mmRetinitis pigmentosa with SAG mutations often shows a characteristic golden sheen surrounding posterior pigmentary retinal degeneration. Oguchi disease can show progressive degeneration in adulthood, rarely resulting in RP.

To determine the potential of anterior-segment optical coherence tomography (AS-OCT) to predict posttrabeculectomy outcomes in neovascular glaucoma (NVG).We recruited 45 eyes of 40 NVG patients who underwent trabeculectomy. The patients were divided into success and failure groups based on the posttrabeculectomy outcome after 12 months. AS-OCT findings were compared in the success and failure groups at 1 and 2 weeks and 1, 3, 6, and 12 months. We also analyzed early posttrabeculectomy bleb parameters with multiple logistic regression, stepwise multiple regression, and the receiver operating characteristic curve to evaluate the power of these parameters to predict long-term outcomes.Intraocular pressure at 6 and 12 months was lower in the success group than the failure group (P0.0016=0.0048). Reflectivity of the bleb wall was higher in the failure group than the success group throughout the study (all: P0.0016). Age and reflectivity of the bleb wall at 1 week were risk factors for failure with odds ratios for failure of 0.91 and 1.67. The area under the receiver operating characteristic curve for reflectivity of the bleb wall at 1 week was 0.943 with the cutoff set at 128.9 (sensitivity: 85.7%; specificity: 100.0%). Stepwise multiple regression analysis showed that reflectivity of the bleb wall at 1 week independently indicated the bleb survival period (β=-0.84; P0.001).AS-OCT-measured reflectivity of the bleb wall, measured at 1 week of trabeculectomy for NVG, might be able to predict of the final status of the bleb.

PurposeTo investigate the clinical significance of color visual acuity (CVA) in preperimetric glaucoma (PPG) and open-angle glaucoma (OAG).MethodsA total of 123 eyes of 73 subjects (22 normal eyes, 14 PPG eyes, and 87 OAG eyes; mean age: 44.9 ± 10.1 years, age range: 21-64 years) were enrolled. CVA was tested for red, green-yellow, blue-green and blue-purple with a newly developed test.ResultsThere was no statistical difference in clinical background factors, including age, sex, intraocular pressure, or spherical equivalent between the three groups. Red VA and blue-green VA were significantly worse in the OAG eyes than in the normal eyes (P = 0.008 and P = 0.015, respectively), although green-yellow VA and blue-purple VA were not significantly worse. Furthermore, red VA and blue-green VA were significantly correlated with MD in a group of eyes with either PPG or OAG (r = -0.23, P = 0.023; r = -0.25, P = 0.012, respectively), but green-yellow VA and blue-purple VA were not.ConclusionRed VA and blue-green VA were detectably worse in eyes with OAG, in close association with the degree of functional loss. This suggests that measuring CVA with the new color test described here may be a promising supplement to existing methods of detecting glaucoma and evaluating its severity.

Purpose The internal limiting membrane (ILM) is a normal part of the retina, and the outcomes of ILM removal have not been fully investigated. ILM flap inversion is a recently developed technique that increases the success rate of macular hole (MH) surgery. Thus, we compared the anatomical closure rate and visual outcome in patients undergoing microincision vitrectomy surgery (MIVS) with ILM flap inversion or conventional ILM peeling for the treatment of MH. Methods The medical records of 90 eyes with MH were reviewed retrospectively. The patients were classified into two groups based on MIVS procedure (group 1: ILM flap inversion, 46 eyes; group 2: ILM peeling, 44 eyes). Results Preoperative characteristics were similar in the two groups, and there were no significant differences in 1 month- or 6 month-postoperative VA between the groups (P = 0.25 and P = 0.42, respectively). However, the surgical success rate was significantly higher in group 1 than group 2 (P = 0.04; 46/46: 100% and 41/44: 93%, respectively). Multiple regression analysis revealed that axial length and MH diameter were independent factors predicting 6-month postoperative BCVA in group 2 (P = 0.001 and P = 0.03, respectively), and that MH diameter was an independent factor predicting 6-month postoperative VA in group 1 (P = 0.03). Logistic regression analysis revealed that axial length (OR = 2.11; P = 0.02; area under the curve: 0.94; cut off score: 28.4 mm) was an independent factor indicating surgical failure in group 2. Conclusion Our results suggest that MIVS with ILM flap inversion might be best suited to treat MH, particularly in patients with high myopia.

To evaluate the association between ocular blood flow and biomarkers of systemic oxidative stress, as well as the potential of these biomarkers to assess normal-tension glaucoma (NTG). This study included 73 eyes of 73 patients with NTG. We assessed ocular blood flow by measuring mean blur rate (MBR) in the optic nerve head using laser speckle flowgraphy, both overall and separately in the vessel and tissue areas. We also measured urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) and skin autofluorescence (SAF), and lastly, determined correlations between these measurements and with other clinical parameters. SAF was correlated with age, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), mean deviation (MD), and overall MBR (P = 0.003, P = 0.013, P = 0.015 and P = 0.006, respectively). SAF and 8-OHdG were both correlated with tissue-area MBR (P = 0.006 and P = 0.010, respectively). Visual acuity, cpRNFLT, mean deviation and tissue-area MBR had a significant tendency to change with NTG severity (P = 0.014, P

Background/aimsTo investigate the relationship between aqueous flare, visual function and macular structures in retinitis pigmentosa (RP).MethodsClinical data from 123 patients with RP (227 eyes), 35 patients with macular dystrophy (68 eyes) and 148 controls (148 eyes) were analysed. The differences in aqueous flare between clinical entities and the correlation between aqueous flare (measured with a laser flare cell meter) versus visual acuity, visual field area (Goldmann perimetry) and macular thickness (optical coherence tomography) in patients with RP were determined. Influence of selected clinical data on flare was assessed using linear mixed-effects model.ResultsAqueous flare was higher in patients with RP than patients with macular dystrophy or controls (p=7.49×E−13). Aqueous flare was correlated with visual field area (R=−0.379, p=3.72×E−9), but not with visual acuity (R=0.083, p=0.215). Macular thickness (R=0.234, p=3.74×E−4), but not foveal thickness (R=0.122, p=0.067), was positively correlated with flare. Flare was not affected by the presence of macular complications. All these associations were maintained when the right and the left eyes were assessed separately. Analysis by linear mixed-effects model revealed that age (p=8.58×E-5), visual field area (p=8.01×E-7) and average macular thickness (p=0.037) were correlated with flare.ConclusionAqueous flare and visual field area were correlated in patients with RP. Aqueous flare may reflect the degree of overall retinal degeneration more closely than the local foveal impairment.

To determine whether anterior-segment optical coherence tomography (AS-OCT) can be used to predict post-trabeculectomy bleb outcomes.We divided 58 eyes of 47 trabeculectomy patients into success or failure groups based on their status at 12 months after surgery. We then compared various AS-OCT measurement parameters between the two groups at 1 and 2 weeks and 1, 3, 6, and 12 months. We also analyzed the early post-trabeculectomy bleb parameters with multiple logistic regression, stepwise multiple regression, and the receiver operating characteristic (ROC) curve, to evaluate the power of these parameters to predict long-term outcomes.Intraocular pressure 3 or more months after trabeculectomy was significantly lower in the success group than the failure group (all: P 0.0016). Cleft volume was significantly higher 6 or more months after trabeculectomy in the success group than the failure group (P = 0.0027 and0.0016). Reflectivity of the bleb wall was significantly higher in the failure group than the success group at 2 weeks and all later time points (all: P 0.0016). Reflectivity of the bleb wall at 2 weeks after trabeculectomy was a risk factor for failure, with an odds ratio (OR) for failure of 2.48 (95% confidence interval, 1.31-4.68, increasing per 10 AU). The area under the ROC curve for reflectivity of the bleb wall at 2 weeks after trabeculectomy was 0.775 when the cutoff value was set at 122.8, with sensitivity, specificity, and OR of 78.3%, 80.0%, and 14.4, respectively. A stepwise multiple regression analysis showed that reflectivity of the bleb wall at 2 weeks was an independent factor indicating postoperative bleb survival period (β = -0.39, P = 0.007).Reflectivity of the bleb wall, measured by AS-OCT, may be an early post-trabeculectomy predictor of bleb outcome.

Purpose Sleep apnoea syndrome (SAS) is often associated with glaucoma, and intermittent hypoxia, present in SAS, can contribute to glaucoma pathogenesis. However, the relationships between SAS, high systemic oxidative stress and the speed of glaucoma progression are unclear. Thus, we investigated these relationships in glaucoma patients with and without SAS. Methods Peripheral blood samples were collected from 166 eyes of 166 Japanese patients: 42 controls, 109 open-angle glaucoma (OAG) patients without SAS and 15 OAG patients with SAS. Prognostic factors for visual field defect progression were determined with logistic regression. Diacron reactive oxygen metabolites (dROM) and biological antioxidant potential (BAP) were measured with a free radical analyser. Clinical parameters were also recorded. Intergroup comparisons used the Mann-Whitney U test. Results Multiple regression analysis showed that SAS was a statistically significant contributing factor to fast visual field defect progression, defined as mean deviation (MD) slope ≤-2.0 dB/Y (SAS: odds ratio (OR) = 14.48; p = 0.002). The non-SAS and SAS groups had similar age, sex, intraocular pressure (IOP), axial length and antiglaucoma drug use. The SAS group had a significantly higher dROM level (p = 0.001), BAP level (p = 0.038) and steeper MD slope (p = 0.001) than the non-SAS group. Conclusion Glaucoma patients with SAS have higher dROM, as well as steeper MD slope, than patients without SAS, suggesting that SAS may induce systemic oxidative stress and promote glaucomatous visual field defect progression.

Endogenous fungal endophthalmitis (EFE) caused by disseminated fusariosis is a rare condition that generally has a poor outcome, even with intensive therapy. Here, we describe a case in which this type of EFE was diagnosed with vitreous sampling and was successfully treated with 25-gauge vitrectomy and antifungals, including liposomal amphotericin B and voriconazole. A 16-year-old male patient undergoing treatment for acute myeloid leukemia complained of eye pain and blurred vision in his right eye. Treatment was initiated for a vitreous opacity, possibly associated with herpetic retinitis, but the patient worsened and he was referred to us. Right-eye visual acuity was limited to light perception. We suspected endogenous endophthalmitis and performed 25-gauge vitrectomy with antibiotic perfusion of ceftazidime, vancomycin, and voriconazole. Vitreous culturing revealed the presence of Fusarium solani species complex, and enhanced computed tomography revealed disseminated fusariosis lesions in the lung, spleen, and the soft tissue of the left upper arm. The patient received antifungal treatment with liposomal amphotericin B and voriconazole, and these conditions were eliminated. Visual acuity recovered to 20/400 after additional vitrectomy for tractional retinal detachment and was maintained at this level during the 6-month follow-up period. The success of our treatment allowed the capture of optical coherence tomography images of the retina during fusarium-associated endogenous endophthalmitis and the follow-up period. Furthermore, this case showed that immediate vitrectomy for suspected EFE and intensive treatment can lead to a good clinical outcome.

Purpose To assess the optic nerve head blood flow (ONH BF) response to hyperoxia in glaucoma patients using laser speckle flowgraphy (LSFG), and determine factors influencing vasoreactivity within the ONH. Methods We performed oxygen provocation testing in 15 eyes of 15 primary open-angle glaucoma (POAG) patients and 15 eyes of 15 age-matched control subjects. During the test, LSFG-derived tissue mean blur rate (MBRT) and clinical variables, including blood pressure, were recorded. We evaluated differences in MBRT alteration during systemic hyperoxia between the groups. Additionally, we calculated the mean % change in MBRT against baseline and determined contributing factors. Results Despite similar clinical variables during systemic hyperoxia in both groups, the mean % change in MBRT against baseline was significantly lower in the POAG than control subjects (P < 0.0001). Multiple regression analysis revealed that baseline MBRT and systolic blood pressure (SBP) were contributing factors to mean % change in MBRT (β = 0.44, β = -0.32, respectively). Additionally, baseline MBRT and SBP were strongly correlated to mean % change in MBRT only in the POAG group (r = 0.83, P < 0.0001; r = -0.60, P = 0.02, respectively). Conclusions POAG patients had a weaker vasoreactive response to hyperoxia than controls, and this impaired response was associated with lower basal ONH BF and higher SBP. These findings suggest that pre-existing vasoconstriction in the ONH of eyes with glaucoma might reduce the capacity of the vasoconstrictive response to hyperoxia. Alternatively, the pathways that mediate hyperoxia-induced vasoconstriction could be altered in POAG.

Purpose To investigate factors associated with choroidal microcirculation in the peripapillary chorioretinal atrophy (PPA) zone in eyes with normal-tension glaucoma (NTG) and myopic disc. Methods In 100 eyes of 100 NTG patients with myopic disc and 20 eyes of 20 age-matched myopic controls, 4.5 × 4.5 mm scans were made of the optic nerve head with optical coherence tomography angiography (OCTA). Peripapillary chorioretinal atrophy (PPA) area and PPA superficial choroidal image intensity (PPA-CI) were calculated with image j software. Clinical characteristics, laser speckle flowgraphy-measured mean blur rate in the temporal tissue area (temporal MT), the central thresholds (the averaged standard automated perimetry-measured visual field thresholds in the four paracentral points) and 3D-OCT-measured ganglion cell complex thickness in the papillomacular bundle (PMB-GCCT) were recorded. Results The NTG patients had significantly lower intraocular pressure, PMB-GCCT and central threshold values, and a larger PPA area, than the controls. The area under the receiver operating characteristics curve to differentiate NTG with parafoveal scotoma (PFS) from controls was 0.76 for temporal MT, 0.85 for PPA-CI and 0.87 for PMB-GCCT. Univariate and multivariate analyses revealed that PPA-CI was negatively correlated with age, pulse rate, best-corrected visual acuity, axial length and PPA area, and positively correlated with temporal MT, PMB-GCCT and the central thresholds. Conclusion Peripapillary chorioretinal atrophy (PPA)-CI was associated with temporal MT, ageing, bradycardia, axial length elongation and changes in central retinal structure and visual function in patients with NTG and myopic disc. Thus, microcirculation deep within the PPA zone might be a clinically useful biomarker of PFS in NTG.

To analyze cytokine profiles of the aqueous humor of eyes with primary open-angle glaucoma (POAG), neovascular glaucoma (NVG), and cataract (as controls).A multiplex bead assay was used to measure concentrations of 27 cytokines in aqueous humor samples from 54 eyes.Detection rates were as follows: IL-7: NVG higher than POAG; IL-10: POAG lower than cataract or NVG; and GM-CSF: cataract higher than POAG or NVG. Concentrations were as follows: IL-8, IP-10, MCP-1, and MIP-1β: POAG and NVG higher than cataract; IL-9: POAG lower than NVG; IL-12: POAG lower than cataract or NVG; and VEGF: NVG higher than cataract or POAG and POAG lower than cataract. Further analysis showed that IL-8, IP-10, MCP-1, and MIP-1β were correlated with intraocular pressure and age.The detection rates and levels of various cytokines had different patterns in POAG and NVG patients, suggesting distinctive alterations in the microenvironment in different types of glaucoma.

To evaluate laser speckle flowgraphy (LSFG) measurements of the optic nerve head (ONH) blood flow (BF) response to hyperoxia.This prospective study included 30 eyes of 30 healthy volunteers (mean age: 28.5 ± 4.0, male:female = 13:17). The testing protocol had three phases: in the baseline phase, subjects breathed room air; in the hyperoxic phase, they breathed pure oxygen (6 L/min) for 15 min; and in the recovery phase, they were room air for 15 min. LSFG measurements of mean blur rate (MBR), which represents ONH BF, were taken every minute. The MBR ratio in the hyperoxic and recovery phases was calculated with reference to this baseline. Clinical parameters, including systemic blood pressure, pulse rate, and saturation of pulse-oximetry oxygen (SpO2), were measured every 5 min.SpO2 increased significantly during hyperoxia (97.3 ± 1.1% to 99.3 ± 0.7%, p 0.001). While clinical parameters were similar in hyperoxia and baseline, MBR decreased significantly after 2 min of hyperoxia (90.8 ± 12.6%, p = 0.02), stayed steady throughout hyperoxia (mean: 89.5 ± 10.8%, p range:0.001-0.04) compared with baseline, and returned to baseline 1 min after recovery (93.7 ± 10.3%, p = 0.25). A linear regression using a third-order polynomial fitting curve analysis revealed that the time to reach minimum MBR was 7.78 min (adjusted R(2 )= 0.87).LSFG could effectively assess ONH BF changes during hyperoxia.

To evaluate the relationship between skin autofluorescence (SAF), which reflects the accumulation of advanced glycation end products (AGEs), and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes.Sixty-seven eyes of 67 patients with type 2 diabetes were enrolled. Sixty-seven age-matched non-diabetic subjects served as controls. Diabetic patients were classified by the severity of their DR: no DR (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). SAF was measured with an autofluorescence reader.SAF in the diabetes patients was significantly higher than in the controls (median 2.5 (interquartile range 2.3-2.7) and 1.8 (1.6-2.3) arbitrary unit (AU), respectively, p 0.001). There was a statistically significant increase in SAF along with the increasing severity of DR (from NDR to NPDR: p = 0.034; NPDR to PDR: p 0.01). Logistic regression analysis revealed that SAF (OR, 17.2; p 0.05) was an independent factor indicating the presence of PDR.SAF has an independent relationship with PDR in patients with type 2 diabetes. SAF measurement with an autofluorescence reader is a non-invasive way to assess the risk of DR. SAF may, therefore, be a surrogate marker candidate for the non-invasive evaluation of DR.

Purpose To investigate sectoral differences in the relationship between optic nerve head tissue blood flow, anatomically corresponding visual field defect severity, and future progression. Methods This retrospective longitudinal medical chart review comprised 508 eyes of 319 open-angle glaucoma patients (mean deviation: -9.2 ± 7.0 dB), followed for an average of 4.7 ± 1.1 years; an average 11.7 ± 3.7 visual field tests were performed. Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 program. The optic nerve head was divided to obtain inferior, temporal, and superior tissue-area mean blur rate (MT), derived from laser speckle flowgraphy. At baseline, the correlation between MT and TD was compared in anatomically corresponding sectors. We performed a multivariate analysis to determine the contribution of baseline MT to corresponding TD slope and to determine background factors influencing superior to temporal MT. We used a linear-mixed effect model for the statistical analysis. Results At baseline, the highest β coefficients were found between MT-superior and TD-inferior, MT-temporal and TD-central, and between MT-inferior and TD-superior, in that order (β = 0.38, β = 0.27, β = 0.26, respectively). MT-superior and MT-temporal independently contributed to corresponding TD slope (P < 0.05). Male sex, high body mass index, and the prevalence of sleep apnea syndrome were contributing factors to lower superior to temporal MT (P < 0.05). Conclusions Review of medical history, measurements of systemic variables, and laser speckle flowgraphy parameters might help clinicians to predict visual field defect severity and progression.

An 81-year-old woman presented with a retinal tumor after unsuccessful surgery was performed for a macular hole (MH) in the 1990s. A histopathological analysis revealed retinal pigment epithelium hyperplasia with no evidence of neoplastic cells. This case highlights two points: first, MHs that remain open after unsuccessful MH surgery can cause retinal tumors, leading to further visual loss; and second, in this case, the MH-associated tumor showed no evidence of neoplastic cells. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:284–286.]

We investigated in detail the correlation between structure and function in the macula, and whether optical coherence tomography (OCT)-measured macular structure could be used to simulate the visual field.This study comprised 60 eyes of 34 patients with open angle glaucoma (Anderson-Patella classification). To assess macular function, reliable data from the Humphrey field analyzer (HFA, SITA-standard, 10-2 program) for threshold, total deviation (TD), and pattern deviation (PD) were used. To assess macular structure, thickness data for the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), and ganglion cell layer plus inner plexiform layer (GCL + IPL) from macular OCT maps (3D OCT-2000, Topcon) were analyzed. Spearman's coefficient of correlation analysis was performed to determine the significance of the correlation, as well as the formula for simulation. The formula was used to calculate the simulated threshold, TD, and PD values. The simulation method was validated by comparing results for simulated and actual visual fields in a new data set of 29 eyes from glaucoma patients.In most test points, macular function and the layer-by-layer structure were significantly correlated, however, the distribution of highly-correlated points varied. Simulated grayscale maps of the visual field based on the formula of regression line for RNFLT and thresholds were similar to actual visual fields. There was a significant correlation between simulated visual fields created from RNFLT, GCC and GCL + IPL data and actual average threshold values in all 68 test points (r = 0.63-0.87, p 0.001) and TD (r = 0.62-0.86, p 0.001).We found that there was a significant correlation between structure and function in the macular area, and that simulated visual fields from RNFLT data reflected actual visual fields. Such a simulation of macular function from OCT parameters may be useful in assessing glaucoma in patients who have difficulty undergoing actual visual field examinations.

To explore methods of automated visual field (VF) examination for the assessment of macular function.We used a VF examination (AP-7000 automatic perimeter, Kowa, Japan) to examine macular function in 53 eyes from 29 patients with open angle glaucoma. We measured the mean total deviation (c-MD) of 16 points in the central VF located in a 2-degree-interval 4 × 4 array with various stimulus sizes (Goldmann sizes III, II, and I). The retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC), and ganglion cell layer plus inner plexiform layer (GCL + IPL) were measured with the 3D OCT-2000 System (Topcon, Japan). The c-MDs of various stimulus sizes were compared with the OCT parameters using the Spearman rank correlation.The average examination time was 93.5 ± 23.5 s and the c-MD values were -11.8 ± 8.2 (stimulus size III), -11.9 ± 9.5 (stimulus size II), and -12.3 ± 9.6 dB (stimulus size I). The c-MD (stimulus size III) and averaged total deviations of the Humphrey Field Analysis 10-2 program were significantly correlated (ρ = 0.91). The C-MD values for stimulus size III were significantly correlated with the OCT parameters (RNFL: ρ = 0.59; GCC: ρ = 0.65; and GCL + IPL: ρ = 0.64). The correlation coefficient between the c-MD and the GCC was better for stimulus sizes II and I (ρ = 0.69) than for stimulus size III (ρ = 0.65).The C-MD values for the 16 measured central VF points were significantly correlated with macular structure, and the smaller stimulus sizes of the automated VF test had a higher correlation coefficient of within 8°.

We investigate the metabolomic profile of reactive persulfides and polysulfides in the aqueous and vitreous humors. Eighteen eyes of 18 consecutive patients with diabetes mellitus (DM) and diabetic retinopathy underwent microincision vitrectomy combined with cataract surgery. Samples of the aqueous and vitreous humors were collected and underwent mass spectrometry-based metabolomic profiling of reactive persulfides and polysulfides (polysulfidomics). The effect of reactive polysulfide species on the viability of immortalized retinal cells (the RGC-5 cell line) under oxidative stress (induced with H2O2) was also evaluated with an Alamar Blue assay. The experiments showed that cysteine persulfides (CysSSH), oxidized glutathione trisulfide (GSSSG) and cystine were elevated in the aqueous humor, and CysSSH, Cys, and cystine were elevated in the vitreous. Furthermore, GSSSG, cystine, and CysSSH levels were correlated in the aqueous and vitreous humors. A comparison, in DM and control subjects, of plasma levels of reactive persulfides and polysulfides showed that they did not differ. In vitro findings revealed that reactive polysulfide species increased cell viability under oxidative stress. Thus, various reactive persulfides and polysulfides appear to be present in the eye, and some reactive sulfide species, which have a protective effect against oxidative stress, are upregulated in the aqueous and vitreous humors of DM eyes.

Purpose There is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost. Method In this study, 122 eyes from 122 subjects (mean age: 53.1 ± 14.3) newly diagnosed as PPG were enrolled. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was evaluated with optical coherence tomography (OCT). The ONH blood flow was measured with laser speckle flowgraphy. The therapeutic effect of Tafluprost was evaluated at Month 0 (ONH blood flow-improving effect) and Month 4 (IOP-lowering effect). Results The untreated IOP, cpRNFLT, and baseline Mean deviation (MD) value was 16.4 ± 2.5 mmHg, 80.4 ± 8.2 μm, and -0.48 ± 1.29 dB, respectively. In the site-specific visual field evaluation using the sector map, there was no appreciable site-specific visual field defect in the eye with PPG. The inferior region of cpRNFLT in 4-quadrant OCT sector analysis and 6 o’clock region in 12-o’clock OCT sector analysis was the highest rate of abnormality in PPG eyes. Topical administration of Tafluprost significantly reduced IOP from 16.4 ± 2.5 mmHg at baseline to 14.5 ± 2.3 mmHg at Month 4 (P < 0.001, paired t-test). In the linear regression analysis, there was a significant relationship between the increase of ONH blood flow and baseline value. Conclusion PPGPS is a first prospective study focusing on the pathology of PPG. This study is expected to elucidate the pathology of PPG, with evidence useful for determining a treatment strategy for PPG.

PURPOSE: To evaluate the efficacy of combined 25-gauge microincision vitrectomy surgery (MIVS) and toric intraocular lens (IOL) implantation with posterior capsulotomy. METHODS: Noncomparative, interventional case series performed at a single center. Twelve patients with vitreoretinal disease and cataracts, with preexisting regular corneal astigmatism greater than 1 diopter, underwent 25-gauge MIVS and toric IOL implantation with posterior capsulotomy. RESULTS: The toric IOL was successfully implanted in each case. At 6 months postoperatively, mean axis rotation was 5.7° ± 3.1°. At 1 month postoperatively, mean uncorrected and best corrected visual acuity improved; the improvement was maintained after 6 months. The absolute residual refractive cylinder was significantly lower postoperatively than the pre-existing regular corneal cylinder ( P = .003). There were no surgical complications except temporary posterior iris synechiae in one case. CONCLUSIONS: Combined 25-gauge MIVS and toric IOL implantation with posterior capsulotomy is a practical and safe method to treat vitreoretinal disease and cataracts with pre-existing corneal astigmatism. [ Ophthalmic Surg Lasers Imaging Retina . 2013;44:145–154]

Purpose Innovative laser speckle flowgraphy (LSFG) enables noninvasive evaluation of retinal microcirculation and the usefulness has been reported in the field of ophthalmology. LSFG has allowed us to measure the real time changes of retinal blood flow without pupillary dilatations and contrast media. Herein, we investigated the change of retinal blood flow in normal pregnant women during gestation using LSFG. Methods A prospective cohort study was conducted in 53 pregnant women who visited our institution between January, 2013 and July, 2014. Finally, a total of 41 participants without any obstetric complications were available for evaluation. Retinal blood flow was measured with LSFG in a total of 4 times during pregnancy (T1. 11-13 weeks, T2. 19-21 weeks, T3. 28-30 weeks, T4. 34-36 weeks) and mean blur rate (MBR), blowout score (BOS), flow acceleration index (FAI), and resistive index (RI) are analyzed from these measurements. Relations between LSFG parameters and mean arterial blood pressure (MAP) are determined throughout pregnancy. Results MBR showed no significant changes throughout pregnancy. BOS showed a tendency to increase in the 3rd trimester. FAI values showed a slight increase from the 1st to 2nd trimester while a significant decrease was noted in the 3rd trimester. RI exhibited no changes between the 1st and 2nd trimesters, values decreased significantly after the 3rd trimester. MAP was positively correlated with BOS, and negatively correlated with FAI and RI. Conclusion The present study clearly demonstrated that profiles of LSFG parameters demonstrated a decrease of resistance in retinal blood vessels. These changes in indices provide a highly sensitive reflection of physiological changes in vascular resistance due to pregnancy. Thus, LSFG may be useful, as a non-invasive, diagnostic tool to detect pregnancy related disorders such as preeclampsia.