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Purpose To report a cluster of cases of toxic anterior-segment syndrome (TASS) in eyes implanted with a specific foldable acrylic intraocular lens (IOL) model. Design Retrospective case series. Methods The medical records were reviewed for 7 eyes of 4 patients diagnosed with TASS after cataract surgery at Shimane University and Matsue Red Cross Hospital between July and November 2020. Results Among the 162 eyes implanted with the Lentis Comfort/LS-313 MF15 IOL, acute anterior chamber (AC) inflammation with fibrin formation developed 1-15 days after uneventful surgeries in 7 (4.3%) eyes (cataract surgery alone, n=4 eyes; combined cataract and minimally invasive glaucoma surgery, n=3 eyes). Other than local steroid use, fibrin membrane removal, YAG laser membranotomy, pars plana vitrectomy, and AC washout were performed to treat inflammation and/or secondary angle closure due to pupillary obstruction. Conclusion We experienced a cluster of TASS cases in eyes implanted with the Lentis Comfort/LS-313 MF15 IOL in a short period of time. To our knowledge, this is the first report of TASS associated with this IOL.

We tested oral French maritime pine bark (40 mg)/bilberry fruit extract (90 mg) supplements for intraocular pressure-lowering effects in Japanese subjects with primary open-angle glaucoma. Eighteen subjects (29 eyes) were recruited with intraocular pressure of ≥15 mmHg who used one to three bottles of antiglaucoma medications. After a 2-week observation (period 1), subjects ingested a tablet/day of Sante® Glagenox for 4 weeks (period 2). The mean intraocular pressure (17.2 ± 2.3 mmHg) decreased significantly to 15.7 ± 1.9 mmHg (8.7% reduction) at week 4 (p = 0.0046). The mean morning intraocular pressure (14.1 ± 3.1 mmHg) self-measured using the iCare HOME tonometer during period 1 decreased significantly to 13.3 ± 2.9 mmHg (5.7% reduction) during period 2 (p = 0.0291). Blood redox parameters, diacron reactive oxygen metabolites, biologic antioxidant potential, and sulfhydryl tests were unchanged after 4-week supplementation. Intra-subject comparisons, compared to period 1, showed pooled, self-measured, period-2 intraocular pressures was significantly lower in nine subjects (50%), unchanged in six subjects (33%), and elevated in three subjects (17%), suggesting some non-responders. Four-week supplementation with French maritime pine bark/bilberry fruit extracts can further reduce intraocular pressure even in Japanese patients with controlled primary open-angle glaucoma. Further study should confirm the intraocular pressure-lowering effects and mechanisms of this supplement in glaucoma management. The study was registered in UMIN (ID: UMIN000033200).

Masaki Tanito,1 Yotaro Matsuoka2 1Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan; 2Division of Ophthalmology, Matsue Red Cross Hospital, Matsue, Shimane, JapanCorrespondence: Masaki Tanito, Department of Ophthalmology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan, Tel +81-853-20-2284, Fax +81-853-20-2278, Email mtanito@med.shimane-u.ac.jpBackground: We report the real-world distribution of glaucoma types and glaucoma surgeries in each age or sex group in our department.Methods: The department database of Matsue Red Cross Hospital, a tertiary care hospital, for eyes surgically treated to manage glaucoma between April 2014 and March 2018 was searched. Patient age, sex, disease type, and surgical procedure were collected from the database. The age was stratified by ≤ 64 years (young), 65– 74 years (pre-old), 75– 89 years (old), and ≥ 90 years (oldest-old or super-old).Results: In the database, 2036 consecutive surgeries (70.3 ± 14.4 years; 1015 males) were identified. Among all subjects, primary open-angle glaucoma (POAG) (42.7%) was the most frequent identifiable glaucoma type followed by primary angle-closure disease (PACD) (18.8%) and exfoliation glaucoma (17.9%). The glaucoma types differed significantly among the age groups (P < 0.0001); POAG was the most frequent type of glaucoma in young and pre-old groups, while PACD and exfoliation glaucoma were the most frequent glaucoma types in the oldest-old group. Among all subjects, trabeculotomy or other goniotomy/gonio-bypass surgery (41.7%) was the most frequent glaucoma surgery followed by long-tube shunt (22.1%) and trabeculectomy (16.2%). The glaucoma surgeries performed differed significantly among the age groups (P < 0.0001). The frequency of trabeculectomy was the highest in the young group (27.8%), trabeculotomy was the highest in the pre-old (42.6%) and old (46.6%) groups, and long tube shunt (41.3%) and cataract extraction + goniosynechialysis (32.6%) were the highest in the oldest-old group. The glaucoma type (P < 0.0001) and surgeries performed (P < 0.0001) differed significantly between sex groups; the rates of PACD and cataract extraction + goniosynechialysis were remarkably higher in female than male group.Conclusion: The types of glaucoma and required glaucoma surgeries differ among the different age groups and sexes. Primary angle-closure disease and exfoliation glaucoma are the major glaucoma types in the old and oldest-old age groups.Keywords: primary open-angle glaucoma, POAG, primary angle-closure disease, PACD, exfoliation glaucoma, trabeculotomy, trabeculectomy, minimally invasive glaucoma surgery, MIGS, cataract extraction

Current therapeutic approaches for glaucoma aim to reduce intraocular pressure (IOP), which is the only available and reliable strategy proven to control the risk of disease development and progression. Omidenepag isopropyl (OMDI) is a novel topical ocular hypotensive agent that was launched onto the market for the treatment of glaucoma and ocular hypertension (OHT). After topical instillation and during corneal penetration, OMDI is converted into the active metabolite omidenepag (OMD), which behaves as a non-prostaglandin, selective E-prostanoid subtype 2 (EP2) receptor agonist. The topical administration of 0.002% OMDI once-daily (QD) possesses a 20-35% IOP-lowering effect, comparable to that of prostaglandin analogs targeting F-prostanoid (FP) receptor QD, which are the current first-line for pharmaceutical reduction of IOP. However, the mechanism of action and adverse events (AEs) of OMDI are different from those of FP receptor agonists. OMDI reduces IOP by enhancing both conventional trabecular and uveoscleral outflow facilities without complications of prostaglandin-associated periorbitopathy (PAP) seen with FP receptor agonists. Moreover, OMDI was also effective and well-tolerated in non-/poor responders to latanoprost and showed a stable IOP-lowering effect for one year, and its concomitant use with timolol enhanced the IOP-lowering effect. OMDI demonstrated acceptable safety and tolerability with good adherence and can be used in almost every patient. However, OMDI has some AEs such as conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema and ocular inflammation. Moreover, OMDI is contraindicated in patients who are allergic to the product, in aphakic or pseudophakic eyes, and in combination with tafluprost eye drops. If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and OHT as a first-line alternative to FP agonists. Here, we summarize the results of clinical studies of OMDI and discuss its efficacy and patient tolerability in glaucoma and OHT in this review.

To assess the roles of preoperative intraocular pressure (IOP) level on the IOP reducing efficacy of microhook ab interno trabeculotomy (µLOT), 126 consecutive open-angle glaucomatous eyes (90 primary open angle glaucoma, 36 exfoliation glaucoma) of 126 Japanese subjects (60 men, 66 women, mean age ± standard deviation, 70.5 ± 11.4 years) who underwent µLOT alone (25 eyes, 20%) or combined µLOT and cataract surgery (101 eyes, 80%) were retrospectively included, and subdivided into four groups based on the quartile of preoperative IOP: Q1, ≤15 mmHg, Q2, 15–18 mmHg, Q3, 18–21 mmHg, and Q4, &gt, 21 mmHg. Preoperative and 12 months postoperative IOPs and numbers of antiglaucoma medications were compared among IOP groups. Factors associated with postoperative IOP were assessed using multivariate analysis, and the success of IOP control was assessed with various definitions. Postoperatively, IOP was significantly higher in Q3 (p &lt, 0.0146) and Q4 (p = 0.0320) groups than Q1 group, while the number of medications was not significantly different among four IOP groups (p = 0.1966). Older age was associated with lower postoperative IOP, and higher preoperative IOP was associated with higher postoperative IOP, while sex, glaucoma type, surgical procedure, lens status, extent of trabeculotomy incision, and preoperative number of medications were not associated with postoperative IOP. The success rates for IOP ≤ 18 and ≤15 mmHg were higher in lower preoperative IOP groups (i.e., Q1 and Q2) than higher preoperative IOP groups (Q3 and Q4), while the success rate for ≥20% IOP reduction was higher in higher preoperative IOP groups than in lower preoperative IOP groups, the success rate for ≥0% IOP reduction was equivalent among groups. By reviewing the previous studies in ab interno trabeculotomy/goniotomy procedures, positive correlation between preoperative and postoperative IOPs was preserved throughout the studies and surgical procedures. After the µLOT, larger %IOP reduction was achieved in higher preoperative IOP groups than in lower preoperative IOP groups, while postoperative IOP was still lower than in lower preoperative IOP groups.

Purpose To compare postsurgical anterior chamber flare (ACF) among conventional (trabeculectomy, LEC) and novel (EX-PRESS Shunt, EXP) filtration surgeries and microhook ab interno trabeculotomy (μLOT), a novel minimally invasive glaucoma surgery (MIGS). Subjects and methods This retrospective study included 125 primary open angle glaucoma eyes (89 consecutive subjects) treated with μLOT (n=38), LEC (n=12), or EXP (n=75). The intraocular pressure (IOP), numbers of antiglaucoma medication, and ACF at preoperatively and 2 weeks; 1, 3, and 6 months postoperatively were compared among the surgical groups using a mixed-effects regression model. Results The postoperative IOP (p

All the 560 glaucomatous eyes of 375 Japanese subjects (181 men, 194 women, mean age ± standard deviation, 76.0 ± 13.2 years) who underwent microhook ab interno trabeculotomy (µLOT) alone (159 eyes, 28%) or combined µLOT and cataract surgery (401 eyes, 72%) performed by one surgeon at Matsue Red Cross Hospital between May 2015 and March 2018 to control intraocular pressure (IOP) were retrospectively assessed. Preoperative and postoperative IOPs, numbers of antiglaucoma medications, the logarithm of the minimum angle of resolution visual acuity (logMAR VA), anterior chamber (AC) flare, visual field mean deviation (MD), and corneal endothelial cell density (CECD) were compared up to 36 months. Surgical complications and required interventions were described. The duration of the follow-up was 405 ± 327 (range, 2–1326) days. The mean preoperative IOP (20.2 ± 7.0 mmHg) and number of antiglaucoma medications (2.8 ± 1.1) decreased to 13.9 ± 4.5 mmHg (31% reduction, p &lt, 0.0001) and 2.5 ± 1.0 (11% reduction, p &lt, 0.0001), respectively, at the final visit. After combined surgery, compared with preoperatively, the final VA improved 0.11 logMAR (p &lt, 0.0001), AC flare increased 4.5 photon counts/msec (p = 0.0011), MD improved 0.6 decibel (p &lt, 0.0001), and the CECD decreased 6% (p &lt, 0.0001). Layered hyphema (172 eyes, 31%) and hyphema washout (26 eyes, 5%) were the most common postoperative complication and intervention, respectively. At the final visit, 379 (69%) eyes achieved successful IOP control of ≤18 mmHg and ≥20% IOP reduction, and 349 (64%) eyes achieved successful IOP control of ≤15 mmHg and ≥20% IOP reduction. Older age, steroid-induced glaucoma, developmental glaucoma, and the absence of postoperative complications were associated with lower final IOP, exfoliation glaucoma, other types of glaucoma, and higher preoperative IOP were associated with higher final IOP. µLOT has a significant IOP-lowering potential in patients with glaucoma, and improves visual function when combined with cataract surgery.

Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women, mean age &plusmn, standard deviation [SD], 68.4 &plusmn, 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 &plusmn, 0.12), the AGE scores were significantly higher in patients with DM (0.59 &plusmn, 0.17, p &lt, 0.0001), NDR (0.58 &plusmn, 0.16, p = 0.0012), and DR (0.60 &plusmn, 0.18, p &lt, 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p &lt, 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p &lt, 0.0001), had worse visual acuity (VA) (p &lt, 0.0001), had higher intraocular pressure (IOP) (p &lt, 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR.

We examined the cytoprotective effect of quercetin via activator protein (AP-1) and the heat shock protein 70 (Hsp70) pathway against light-induced retinal degeneration in rats. Quercetin was administered intraperitoneally to Sprague-Dawley rats for seven days before light exposure to intense white fluorescent light (3000 lux) for 24 h. Light-induced retinal damage was determined by the number of rows of photoreceptor cell nuclei, the microstructures of the rod outer segments and retinal pigment epithelium, and terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine-5'-triphosphate (dUTP) nick end labeling. To elucidate the cytoprotective mechanism of quercetin, expression levels were measured in the rat retinas of 8-hydroxy-deoxyguanosine (8-OHdG), a marker of oxidative stress; Hsp70; and transcription factor AP-1 transcription activity. Pretreatment with quercetin inhibited light-induced photoreceptor cellular apoptosis and subsequent retinal degeneration in rats. 8-OHdG and Hsp70 protein expressions were up-regulated markedly by light exposure and suppressed by quercetin pretreatment. The results of an electrophoretic mobility shift assay showed that AP-1-binding activity was activated by light exposure, and binding of c-Fos and c-Jun, but not JunB, mediated the binding activity. Intraperitoneal administration of quercetin decreases photooxidative damage in the retina and mediates cytoprotection against light-induced photoreceptor cell degeneration in rats. Suppression of the heterodimeric combination of c-Jun and c-Fos proteins at the AP-1 binding site is highly involved in quercetin-mediated cytoprotection.

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

Purpose To report the efficacy of systemic prostaglandin E1 (PGE1) monotherapy for treating acute central retinal artery occlusion (CRAO). Methods The best-corrected visual acuity (BCVA) and side effects were evaluated retrospectively in 10 consecutive eyes (nine patients; mean age, 61.3 years) with acute CRAO treated with PGE1 monotherapy. The protocol included intravenous injection of 40 μg PGE1 twice daily (80 μg per day) for 5 days then oral PGE1 three times daily (30 μg per day) for at least 1 month. In four eyes, the retinal vessel diameters were assessed on serial fundus photographs. Results The mean time to treatment was 7.1 hours (range, 1-18 hours). The mean ± SD logarithm of the minimum angle of resolution (logMAR) BCVAs at baseline and 1 month after initiation of therapy were 2.67 ± 0.54 (range, 3.00-1.70) and 0.52 ± 0.62 (range, 2.00 to -0.18), respectively (P = 0.005); the BCVA improved by 1.0 or more logMAR unit at 1 month in all eyes. The BCVA improvement was correlated negatively with the time to treatment (ρ = -0.655, P = 0.0492), but was not correlated with age (ρ = -0.473, P = 0.156) and did not differ between sexes (P = 0.0871). Compared with baseline, the mean changes in the vessel diameters in four cases were 151.1% (range, 115.1%-188.0%) in the arteries and 191.0% (range, 127.2%-246.4%) in the veins 1 day after initiation of therapy. Angialgia during injection was the only side effect. Conclusions Systemic administration of PGE1 for acute CRAO rapidly restores retinal blood flow by its vasodilatory effects, improves VA, is well tolerated with few side effects, and requires no special training.

Purpose To test the safety and efficacy of topical 1.5% dexamethasone aqueous eye drops with cyclodextrin microparticles for diabetic macular edema (DME). Methods Nineteen eyes of 19 consecutive patients with DME were administered dexamethasone-cyclodextrin eye drops three or six times a day for 4 weeks and then observed for 4 weeks without treatment. Visual acuity, intraocular pressure, and spectral domain optical coherent tomography-measured central macular thickness recordings at weeks 0 (baseline), 4, and 8. These parameters were compared using Bonferroni-corrected paired t-tests. Results At weeks 0, 4, and 8, logMAR visual acuity (mean ± SD) was 0.52 ± 0.41, 0.37 ± 0.40 (P = 0.0025 vs. baseline), and 0.45 ± 0.41, respectively; central macular thickness (μm) was 512 ± 164, 399 ± 154 (P = 0.0016 vs. baseline), and 488 ± 172 (P = 0.0116 versus week 4), respectively; and intraocular pressure (mm Hg) was 15.2 ± 3.1, 17.4 ± 4.2 (P = 0.0015 vs. baseline) and 15.8 ± 4.0, respectively. At week 4, in 12 (63%) of 19 eyes, central macular thickness had decreased more than 10%, and the mean change was -20% (-65% to +10%). In 14 of 19 eyes (74%) visual acuity (logMAR) had improved more than 0.1 at week 4. No subjects showed severe adverse effects related to the eye drops. Conclusions Based on this short pilot study, topical dexamethasone-cyclodextrin eye drops are well tolerated, decrease central macular thickness, and improve visual acuity in DME. The results encourage comparative studies between dexamethasone cyclodextrin microparticle eye drops and other treatments for DME. (http://www.umin.ac.jp/ctr number, UMIN000001790.).

PURPOSE Toevaluate the effect of removing epiretinal membranes (ERMs) on visual function and vision-related quality of life (VR-QOL) for 12 months postoperatively. METHODS Idiopathic ERMs were removed during vitrectomy in 26 eyes. The VR-QOL was evaluated using a self-administered 25-item National Eye Institute Visual Function Questionnaire before (baseline) and 3 and 12 months postoperatively. During the same periods, the best-corrected visual acuity (BCVA), central macular thickness (CMT), and metamorphopsia score were recorded. RESULTS At baseline and months 3 and 12, the logMAR BCVAs (mean ± SEM) were 0.41 ± 0.05, 0.17 ± 0.04 (P = 0.0001 versus baseline), and 0.10 ± 0.03 (P < 0.0001 versus baseline, P = 0.0016 versus month 3), respectively; the CMTs (μm) were 402 ± 18, 312 ± 9 (P < 0.0001 versus baseline), and 300 ± 7 (P < 0.0001 versus baseline, P = 0.0544 versus month 3); and the metamorphopsia scores were 202 ± 29, 137 ± 27 (P = 0.0186 versus baseline), and 108 ± 26 (P = 0.0005 versus baseline, P = 0.0218 versus month 3). In 23 (88%) of 26 eyes, the BCVA improved more than 0.1 logMAR unit at month 12. The improved BCVA was correlated with improvements in two subscales (r = -0.405 to -0.574, P = 0.0041-0.0427) at month 3; the improved metamorphopsia score was correlated with the improved composite score (r = -0.552, P = 0.0058) and three subscales (r = -0.458 to -0.507, P = 0.0113-0.0219) at month 12. CONCLUSIONS Removing ERMs improved visual function, anatomy, and the VR-QOL. Three months postoperatively, the improved BCVA was the most important factor related to the improved VR-QOL, although the simultaneous cataract surgery might have had a confounding effect. The improved metamorphopsia was the important factor associated with improved VR-QOL 12 months postoperatively.(www.umin.ac.jp/ctr number, UMIN000000617).