Phosphorylation of αB-Crystallin Involves Interleukin-1ß-Mediated Intracellular Retention in Retinal Müller Cells: A New Mechanism Underlying Fibrovascular Membrane Formation.

Purpose: Chronic inflammation plays a pivotal role in the pathology of proliferative diabetic retinopathy (PDR), in which biological alterations of retinal glial cells are one of the key elements. The phosphorylation of αB-crystallin/CRYAB modulates its molecular dynamics and chaperone activity, and attenuates αB-crystallin secretion via exosomes. In this study, we investigated the effect of phosphorylated αB-crystallin in retinal Müller cells on diabetic mimicking conditions, including interleukin (IL)-1ß stimuli. Methods: Human retinal Müller cells (MIO-M1) were used to examine gene and protein expressions with real-time quantitative PCR, enzyme linked immunosorbent assay (ELISA), and immunoblot analyses. Cell apoptosis was assessed by Caspase-3/7 assay and TdT-mediated dUTP nick-end labeling staining. Retinal tissues isolated from the Spontaneously Diabetic Torii (SDT) fatty rat, a type 2 diabetic animal model with obesity, and fibrovascular membranes from patients with PDR were examined by double-staining immunofluorescence. Results: CRYAB mRNA was downregulated in MIO-M1 cells with the addition of 10 ng/mL IL-1ß; however, intracellular αB-crystallin protein levels were maintained. The αB-crystallin serine 59 (Ser59) residue was phosphorylated with IL-1ß application in MIO-M1 cells. Cell apoptosis in MIO-M1 cells was induced by CRYAB knockdown. Immunoreactivity for Ser59-phosphorylated αB-crystallin and glial fibrillary acidic protein was colocalized in glial cells of SDT fatty rats and fibrovascular membranes. Conclusions: The Ser59 phosphorylation of αB-crystallin was modulated by IL-1ß in Müller cells under diabetic mimicking inflammatory conditions, suggesting that αB-crystallin contributes to the pathogenesis of PDR through an anti-apoptotic effect.

Reduction of Intraocular Pressure and Aqueous Outflow Resistance After Modified 360-degree Suture Trabeculotomy.

PRCIS: Decreasing aqueous outflow resistance at trabecular meshwork is the main mechanism of modified 360-degree suture trabeculotomy (ST), and the preoperative C-value, which shows aqueous outflow resistance, is likely to be useful for predicting intraocular pressure (IOP) reduction. PURPOSE: To clarify the mechanism of IOP reduction and the preoperative prognostic predictor of modified 360-degree ST. MATERIALS AND METHODS: Forty-three eyes of 32 patients with glaucoma who underwent ST at Hokkaido University Hospital between April 2017 and February 2020 were enrolled. The records of postoperative IOP and coefficient of aqueous outflow (C-value) after ST were reviewed from clinical charts retrospectively. Preoperative IOP and C-values were also reviewed and considered as the baseline. RESULTS: Although the differences were not significant, IOP decreased to 15.4±3.3 mm Hg at 3 months ( P =0.10) and 16.1±3.8 mm Hg at 6 months ( P =0.21). In addition, there were significant decreases in anti-glaucoma medication scores at both 3 and 6 months after surgery ( P <0.01). The C-value increased significantly to 0.24±0.11 µL/min/mm Hg at 3 months ( P <0.01) and increased significantly to 0.27±0.14 µL/min/mm Hg at 6 months ( P <0.01). The rates of change in IOP were negatively correlated with that in the C-value at 3 months ( r =-0.49 P <0.01) and 6 months ( r =-0.46 P <0.01). The success rate (IOP<21 mm Hg, IOP reduction>20%) was greater in the low baseline C-value group (≤0.17) than high baseline C-value group (>0.17) ( P <0.05), and the baseline IOP and C-values were statistically significant in association with the success ( P <0.05) at 6 months. CONCLUSIONS: Increased conventional outflow by the elimination of the aqueous outflow resistance at the trabecular meshwork is the main mechanism of IOP reduction after ST. Preoperative examination of tonographic outflow facility may be useful for predicting the IOP reduction and outcome of ST.

Long-term Outcomes of Modified 360-Degree Suture Trabeculotomy for Uveitic Glaucoma Compared With Primary Open Angle Glaucoma.

PRCIS: A Kaplan-Meier survival curve analysis showed no significant differences in success rates between uveitic glaucoma (UG) and primary open angle glaucoma (POAG) 120 months after modified 360-degree suture trabeculotomy, which was effective for both groups in the long term. PURPOSE: The aim of this study was to examine the outcomes of modified 360-degree suture trabeculotomy in patients with UG as compared with those with POAG. PATIENTS AND METHODS: This was a retrospective, nonrandomized, and comparative case series study. Modified 360-degree trabeculotomy using a 5-0 nylon suture (S-LOT) was performed on 51 eyes of 51 patients (54.4±13.4 y) with UG between October 2005 and January 2012 at Hokkaido University Hospital. Age-matched patients with POAG who underwent S-LOT during the same period were enrolled as controls. Written informed consent was obtained from all patients enrolled in the present study. Surgical success was defined as an intraocular pressure (IOP) <18 mm Hg with similar or lower doses of antiglaucoma medications. Kaplan-Meier survival curves of surgical failure were analyzed and compared between UG and POAG. RESULTS: The mean follow-up periods (±SD) for UG and POAG were 104.8±44.0 and 98.1±36.3 months ( P =0.23), respectively. Mean preoperative IOP in UG and POAG were 34.9±11.0 and 25.3±9.4 mm Hg ( P <0.001), respectively. After surgery, mean IOP in UG and POAG decreased to 12.0±4.1 and 13.8±3.2 mm Hg, respectively, at 60 months, and 12.1±5.6 and 12.4±1.8 mm Hg ( P =0.86), respectively, at 120 months. The Kaplan-Meier survival curve analysis showed no significant differences in success rates between UG and POAG at the end of the follow-up (Log-rank test, P =0.13). Success rates in UG and POAG were 70.0 and 62.5% at 60 months, and 67.5 and 41.2% at 120 months, respectively. CONCLUSION: These results suggest that S-LOT is effective for UG and POAG alike.

Surgical outcomes of partial ciliary body direct suturing under the scleral flap for traumatic cyclodialysis cleft: A five-case series.

BACKGROUND: Cyclodialysis cleft is an uncommon finding due to blunt ocular trauma. A larger and more chronic cyclodialysis requires surgical repair. The aim of this study was to introduce a minimally invasive suturing technique for the lens-sparing repair of traumatic cyclodialysis cleft and evaluate outcomes. METHODS: This study was a retrospective case series. The medical and surgical records of five patients with traumatic cyclodialysis cleft who underwent this surgery were reviewed. The surgeon (Y.S.) dissected a fornix-based conjunctival flap and created a 90° circumferential and limbal-based scleral flap. Several small incisions parallel to the limbus were made within the scleral bed 1.5 and 3 mm posterior to the limbus. After suprachoroidal fluid drainage, tiny bumps in the ciliary body were exposed from the incisions and sewn directly onto the scleral bed with 10-0 nylon sutures. RESULTS: The mean age of the patients was 37.8 ± 1.3 years. The mean duration from injury to surgery was 14.8 ± 16.7 months. Mean best-corrected visual acuity (BCVA) was 0.56 ± 0.70 and intraocular pressure (IOP) was 5.2 ± 1.9 mmHg. In all patients, IOP normalized and BCVA then returned to baseline following this procedure. Mean postoperative BCVA was 1.17 ± 0.86 and IOP was 17.8 ± 1.3 mmHg. Mean IOP and BCVA recovery times were 82.0 ± 139.6 and 294.3 ± 284.3 days, respectively. CONCLUSIONS: Partial ciliary body direct suturing under the scleral flap is a less invasive surgical option without lensectomy and considered safe and effective as a primary surgical repair for traumatic cyclodialysis cleft.

Cerebrospinal fluid hypovolemia syndrome mimicking ocular myasthenia gravis: A case report.

Purpose: Cerebrospinal fluid hypovolemia syndrome (CHS) is a rare clinical entity that can be caused by spontaneous cerebrospinal fluid (CSF) leakage. The aim of this study is to report a rare case of CHS after a traffic accident in a patient who presented with diplopia and ptosis with fluctuation and was initially diagnosed with ocular myasthenia gravis. Observeations: A 29-year-old man exhibited fluctuating left ptosis and diplopia after a traffic accident. Although he was suspected of having myasthenia gravis and was treated using oral pyridostigmine bromide, his symptoms did not improve. He also had orthostatic headaches and malaise after the accident. His symptoms were suspected to be associated with traumatic cerebrospinal fluid hypovolemia. After 1000-mL fluid replacement, his diplopia and ptosis improved, and orbital T2-weghted MRI detected a high-signal zone around the optic nerve. We diagnosed him with oculomotor nerve paresis associated with cerebrospinal fluid hypovolemia. The symptoms, including ptosis, diplopia, orthostatic headaches, and malaise, disappeared after epidural blood patch therapy. Conclusions and Importance: When treating patients with fluctuating ocular symptoms, such as diplopia and ptosis, who have a history of trauma and orthostatic headaches, the possibility of CHS should be considered in the differential diagnosis.

Surgical Outcomes of Trabeculectomy in Uveitic Glaucoma: A Long-Term, Single-Center, Retrospective Case-Control Study.

PURPOSE: To evaluate the long-term outcomes of trabeculectomy with mitomycin C (MMC-TLE) in patients with uveitic glaucoma (UG). Patients and Methods. This was a retrospective, nonrandomized case series study. MMC-TLE was performed on 50 eyes with UG between February 2001 and January 2015 at Hokkaido University Hospital. Age- and sex-matched patients with primary open angle glaucoma (POAG) who underwent MMC-TLE were matched by age and sex and enrolled as controls. Surgical success was defined as an intraocular pressure (IOP) less than 18 or 15 mmHg. The Kaplan-Meier survival curves for surgical failure were analyzed. RESULTS: The mean preoperative IOP in UG and POAG was 27.6 ± 10.6 and 18.0 ± 4.5 mmHg, respectively. After the surgery, the mean IOP in UG and POAG was reduced to 11.7 ± 4.2 and 12.2 ± 3.8 mmHg at 12 months, 11.9 ± 7.0 and 12.1 ± 3.1 mmHg at 36 months, and 13.0 ± 5.2 and 10.6 ± 1.2 mmHg at 120 months, respectively. The success rates (IOP <18 mmHg, IOP reduction >20%) in UG and POAG were 91.7% and 88.0% at 12 months, 82.2% and 75.6% at 36 months, and 66.5% and 61.8% at 120 months, respectively. The success rates (IOP <15 mmHg) in UG and POAG were 64.0% and 58.0% at 12 months, 55.1% and 45.5% at 36 months, and 47.9% and 37.8% at 120 months, respectively. There was no significant difference in the success rate between UG and POAG at 120 months after surgery by either definition of surgical success. CONCLUSIONS: MMC-TLE effectively reduced IOP in both UG and POAG. There was no significant difference in the success rate between UG and POAG. Following sufficient inflammation suppression, surgical outcomes of UG may be comparable with those of POAG.

Optical coherence tomography as a possible tool to monitor and predict disease progression in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

Optical coherence tomography (OCT) is an imaging technique used to obtain three-dimensional information on the retina. In this article, we evaluated the structural neuro-retinal abnormalities, especially the thickness in the ganglion cell complex (GCC), in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The GCC thickness in MELAS patients was significantly thinner than that in normal controls even when they had no history of transient homonymous hemianopia. There was a negative correlation between GCC thickness and disease duration. In conclusion, OCT may be an effective tool to monitor and predict disease progression in MELAS patients.

Morphological features of macular telangiectasia type 2 in Japanese patients.

PURPOSE: This study aimed to demonstrate the clinical course of Japanese patients with macular telangiectasia type 2 (MacTel-2). METHODS: This retrospective observational case series included 16 eyes of 8 Japanese patients (3 men and 5 women) with MacTel-2. The mean age and follow-up duration was 66.9 years and 42.8 months, respectively. Differences in best-corrected visual acuity (BCVA), funduscopic macular findings, central macular thickness (CMT), and the length of macular ellipsoid zone (EZ) loss were compared between the initial/baseline and final visits. Optical coherence tomographic changes in CMT by ≥ 20% and in EZ loss by ≥ 20% or ≥ 100 µm were defined as improved or worsened. RESULTS: Numerical changes in BCVA and EZ loss during follow-up were not statistically significant. However, the mean CMT at baseline, which was lower than that of healthy control eyes (P < 0.001), significantly increased during follow-up (P = 0.041). A certain proportion of eyes showed improvement in several parameters: funduscopic findings (both parafoveal retinal graying and foveal retinal pigment epithelium depigmentation) in 29% of eyes, CMT in 21% of eyes, and EZ loss in 43% of eyes. CONCLUSIONS: The non-negligible proportion of eyes with improved parameters, marked especially by macular EZ loss, suggests that Japanese patients with MacTel-2 have milder clinical features than Caucasian patients reported in the literature.

Cerebrospinal fluid hypovolemia syndrome after a traffic accident with abnormal eye movements: A case report.

PURPOSE: To describe a rare case of cerebrospinal fluid hypovolemia syndrome after a traffic accident with abnormal eye movements. OBSERVATIONS: A 19-year-old man was referred to our clinic after being hit by a car five months ago while riding a bicycle. After the accident, he sometimes noticed oscillopsia, and had postural headaches and reading difficulties. His eye movement recording revealed square wave jerks during fixation and decreased pursuit gain during horizontal smooth pursuit. MR myelography detected cerebrospinal fluid leakage and the patient was diagnosed with cerebrospinal fluid hypovolemia. After undergoing epidural blood patch therapy, the leakage disappeared, and his postural headaches improved immediately. Square wave jerks and decreased pursuit gain improved, and his oscillopsia and reading difficulty also improved after therapy. CONCLUSIONS AND IMPORTANCE: A patient with cerebrospinal fluid hypovolemia presented with square wave jerks and decreased pursuit gain. Epidural blood patch therapy was effective for the symptoms. When treating patients with oscillopsia and postural headaches, we should consider the possibility of cerebrospinal fluid hypovolemia syndrome in the differential diagnosis.

Improvements in visual acuity and macular morphology following cessation of anti-estrogen drugs in a patient with anti-estrogen maculopathy resembling macular telangiectasia type 2: a pathogenic hypothesis.

BACKGROUND: The relationship between anti-estrogen drugs and macular telangiectasia type 2 (MacTel-2) remains unknown. Here we report a case with anti-estrogen maculopathy resembling MacTel-2 with improved visual function and macular morphology following cessation of anti-estrogen drugs. CASE PRESENTATION: A 53-year-old woman presented with a 5-month history of central vision loss and anorthopia in both eyes. She had received oral tamoxifen followed by toremifene for 69 months. Funduscopy, fluorescein angiography, and optical coherence tomography (OCT) revealed MacTel-2-like findings OU. Fundus autofluorescence (FAF) showed hyper-autofluorescence at the fovea OU. Visual acuity, macular morphology on OCT, and FAF findings gradually improved after cessation of anti-estrogen drugs. CONCLUSIONS: In the present case, visual acuity, macular morphology, and impairment of the retinal pigment epithelium (RPE) improved following cessation of anti-estrogen drugs, suggesting the relationship between retinal toxicity of anti-estrogen drugs and the development of MacTel-2-like findings. From these results and the previous observations, toxicity of both photoreceptor and RPE cells caused by anti-estrogen drugs may contribute to the development of anti-estrogen maculopathy similar to MacTel-2.