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.

Histological analysis of trabeculotomy - An investigation on the intraocular pressure lowering mechanism.

The primary aim of trabeculotomy (TLO) and/or minimally invasive glaucoma surgery (MIGS) is to produce a direct communication between the anterior chamber (AC) and collector channels (CC), which is believed to be the process by which intraocular pressure (IOP) is normalized. However, we previously reported our finding of the large opening of the Schlemm's canal (SC) into the AC in eyes with failed TLO (Amari et al., 2015). If the routes from the AC to the CC by TLO/MIGS are direct, IOP should be stabilized at around aqueous vein pressure if the SC and CC are undamaged. However, in eyes in which TLO/MIGS is successful, IOP usually stays at around the middle or high teens post surgery. In this current study, we retrospectively investigated the specific reason for middle- or high-teens IOP following TLO/MIGS via the histological examination of trabeculectomy (TRAB) specimens that include the area of previous TLO/MIGS in eyes with failed TLO or insufficient IOP control following TLO by specifically focusing on the behavior of the SC endothelium (SCE). Patient background, maximum IOP prior to TLO/MIGS and TRAB, the number medications administered, and elapsed time between TLO/MIGS and TRAB were reviewed. In 42 TRAB specimens of 31 120-180° TLO eyes (Group A; 27 ab-externo and 4 ab-interno eyes) and 11 360° suture TLO eyes (Group B), SC length (SCL), the site of the incision in the trabecular meshwork (TM) [i.e., the center (CEN)/anterior-tip (TIP)], and TM opening into the AC [i.e., open (OPN)/closed (CLS)] were histologically investigated. The correlation between the clinical parameters of the maximum IOP of pre-TLO/MIGS, the maximum IOP of pre-TRAB, the percentage of IOP reduction (PIR), and the histological results were statistically evaluated. Our findings revealed a significant negative correlation between the maximum IOP of pre-TRAB and SCL (P = 0.0167), and a significantly higher PIR in the eyes with OPN than those with CLS in Group A (P = 0.0045). However, no significant difference in SCL was found between the OPN and CLS eyes in both groups. In comparison to Group A, a higher percentage of OPN (82%) yet a smaller SCL (P = 0.0024) was observed in Group B. No significant correlation between clinical and histological parameters was found in Group B. In both groups, the common finding was sealing of the SC openings by SC endothelium (SCE) and no direct communication between the AC and the CC. This fact indicates that the nature by which SCE seals off the opened SC lumen into the AC created by TLO may be very important for maintaining the blood-aqueous barrier. Based on these results, we concluded that accessibility for aqueous humor to the SC and preservation of the SC may be important for lowering IOP by TLO. However, the opening of the SC into the AC (OPN type) does not guarantee an adequate IOP lowering effect if the SC is widely collapsed. Thus, TLO may be improved only by eliminating the most resistant part of the TM with minimal SCE damage.

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.

Expression of Vascular Endothelial Growth Factor-C in the Trabecular Meshwork of Patients with Neovascular Glaucoma and Primary Open-Angle Glaucoma.

To investigate the expression of vascular endothelial growth factor (VEGF)-C and vascular endothelial growth factor receptor (VEGFR)3 in the trabecular meshwork (TM) of patients with glaucoma and cultured TM cells. Methods: The expressions of VEGF-C in angle tissues collected by trabeculectomy from patients with glaucoma and non-glaucomatous choroidal malignant melanoma were analyzed by immunohistochemistry. Additionally, VEGF-C concentrations were determined in the aqueous humor of patients with glaucoma by ELISA. The expressions of VEGFR3, which is a receptor of VEGF-C in cultured TM cells, were analyzed by Western blot analysis and immunocytochemistry. Cultured TM cells were stimulated by oxidative stress, hypoxia, or high glucose conditions, and VEGF-C concentrations in supernatants and cell lysates were determined by ELISA. Results: VEGF-C immunoreactivity was positive in TM tissues of glaucoma patients, but not in those of non-glaucomatous controls. VEGF-C concentrations in the aqueous humor of patients with neovascular glaucoma and primary open-angle glaucoma were lower than those with non-glaucoma patients. VEGFR3 was expressed in cultured TM cells. VEGF-C concentrations in supernatants or cell lysates of TM cells cultured under oxidative stress and hypoxia were significantly elevated compared with those under steady conditions (p < 0.05). VEGF-C concentrations in supernatants and cell lysates of TM cells cultured in high glucose were significantly higher than those in low glucose (p < 0.01). Conclusions: VEGF-C was expressed in TM tissues of patients with glaucoma, which was secreted from cultured TM cells under various pathological conditions. These results suggest that VEGF-C may be involved in the pathology of glaucoma.

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.

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.

Cytoprotective Effect of Astaxanthin in a Model of Normal Intraocular Pressure Glaucoma.

Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies. Lowering intraocular pressure is currently the only way to treat glaucoma, but it is often insufficient to inhibit the progression of the disease. Glaucoma is a multifactorial disease, and the involvement of oxidative stress has recently received much attention. In the present study, we investigated the cytoprotective effect of astaxanthin (AST) on RGC degeneration using a normal-tension glaucoma (NTG) mouse model, which lacks the glutamate/aspartate transporter (Glast) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure. Three-week-old Glast± mice were given intraperitoneal injections of AST at 10, 30, or 60 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. Five weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. We also used a retrograde labeling technique to quantify the number of RGCs. Additionally, the phosphorylated (p) IκB/total IκB ratio and the 4-hydroxynonenal (HNE) were measured in retinal tissues. The number of RGCs in Glast± mice was significantly decreased compared with that in control mice. RGC loss was suppressed by the administration of AST at 60 mg/kg/day, compared with vehicle alone. Following AST administration, the concentration of 4-HNE in the retina was also suppressed, but the pIκB/IκB ratio did not change. Our study revealed that the antioxidative stress effects of AST inhibit RGC degeneration in the retina and may be useful in the treatment of NTG.

Receptor-Associated Prorenin System in the Trabecular Meshwork of Patients with Primary Open-Angle Glaucoma and Neovascular Glaucoma.

The receptor-associated prorenin system (RAPS) is associated with several pathologic conditions, including diabetic retinopathy, age-related macular degeneration, and uveitis. Here, we show the involvement of RAPS in the trabecular meshwork (TM) from patients with primary open-angle glaucoma (POAG) and neovascular glaucoma (NVG) due to proliferative diabetic retinopathy. Anterior chamber (AC) levels of prorenin significantly increased in both POAG and NVG, as did those of angiotensin II in NVG alone, compared to cataract. In surgically excised TM tissues, (pro)renin receptor ((P)RR) and angiotensin II type 1 receptor (AT1R) co-localized with prorenin and angiotensinogen, respectively. In screening for various genes related to glaucoma, prorenin stimulation to human TM cells exclusively upregulated cell junction constituents connexin 43 and zona occludens 1, while downregulating an extracellular matrix-degrading enzyme tissue plasminogen activator, all of which were reversed by (P)RR blockade. In contrast, angiotensin II application upregulated a pro-angiogenic factor placental growth factor alone, which was abolished by AT1R blockade. Consistently, (P)RR and AT1R co-localized with these corresponding proteins in patient TM tissues. Oxidative stress, a known etiology for glaucoma, induced the expression of prorenin and angiotensinogen in human TM cells. These data suggest the contribution of RAPS to the molecular pathogenesis of POAG and NVG through TM tissue remodeling and AC angle angiogenesis.

Sudden bilateral vision loss due to third ventricular cavernous angioma with intratumoral hemorrhage - case report.

BACKGROUND: We report a rare case of sudden bilateral vision loss due to third ventricular cavernous angioma with intratumoral hemorrhage. CASE PRESENTATION: A 45-year-old woman presented decreased visual acuity in both eyes. Her best corrected visual acuity was 0.1 in the right eye and 0.15 in the left eye. Goldmann perimetry showed bilateral central scotomas and bitemporal visual field defects. MRI demonstrated a lesion with mixed hypo- and hyperintensity at the optic chiasm, which was thought to be an intratumoral hemorrhage. The patient underwent bifrontal craniotomy. The tumor was exposed via an anterior interhemispheric approach, and histological evaluation of the mass led to a diagnosis of cavernous angioma. Six months after the surgery, her best corrected visual acuity was 0.9 in the right eye and 0.9 in the left, with slight bitemporal visual field defects. CONCLUSION: Third ventricular cavernous angioma is considered in the differential diagnosis of chiasmal syndrome. Contrast-enhanced MRI and FDG-PET might be useful for differential diagnosis of cavernous angioma from other chiasmal tumors including glioblastoma.

Changes in Intraocular Pressure in Single Ventricle Patients After the Glenn or Fontan Procedure.

PRéCIS:: A positive correlation was observed between intraocular pressure (IOP) and central venous pressure (CVP) in patients with single ventricle (SV) during the perioperative period. IOP needs to be carefully monitored in the postoperative period after the Glenn and Fontan procedures, particularly the Glenn procedure. PURPOSE: SV is a cardiac malformation characterized by the existence of only 1 functional ventricle and is treated using the Glenn and Fontan procedures. Significant changes occur in CVP after these procedures. IOP has been reported to differ in the same individual when measured in a seated or supine position, which may be related to CVP. In the present study, we examined the relationship between CVP and IOP before and after surgery for SV. PATIENTS AND METHODS: This study was a prospective, nonrandomized case series. All patients had SV and this study excluded those with eye diseases associated with ocular hypertension. We measured IOP before and after the Glenn or Fontan procedure. CVP was concurrently monitored. RESULTS: Twenty-eight eyes of 14 patients with SV who underwent the Glenn (N=8) or Fontan (N=6) procedure were examined. Mean ages (±SD) were 2.6±0.7 months for the Glenn procedure and 24.0±2.7 months for the Fontan procedure. A correlation was observed between CVP and IOP in the perioperative period. IOP and CVP were both significantly higher after than before the Glenn and/or Fontan procedures. However, no relationship was noted between changes in IOP and CVP after the Glenn and/or Fontan procedures. CONCLUSIONS: Elevations in CVP significantly increased IOP in patients with SV who underwent the Glenn or Fontan procedure. IOP needs to be carefully monitored in the postoperative period after both procedures.

Histological Findings in the Trabecular Meshwork of a Patient with Atopic Glaucoma.

PURPOSE: The aim of this study was to report a case of atopic dermatitis showing elevated intraocular pressure (IOP) beyond the baseline levels followed by a modified 360-degree suture trabeculotomy, and to analyze the histological findings in the trabecular meshwork. METHODS: A 40-year-old male suffered from blurred vision in the right eye (OD). He had a medical history of severe atopic dermatitis and intraocular lens implantation OU due to atopic cataract. At the initial presentation, the visual acuity was 0.03, and IOP was 35 mmHg OD. Slit-lamp examination demonstrated corneal epithelial edema OD. Increased IOP was refractory to several topical medications. The patient underwent a modified 360-degree suture trabeculotomy. The visual field defect, however, deteriorated with persistently high IOP. The patient underwent trabeculectomy together with drainage implant surgery. In the outflow routes, although there seemed to be an opening of Schlemm's canal into the anterior chamber, there was no endothelium of the canal in the region of its opening. The fibrotic changes were conspicuous around Schlemm's canal. CONCLUSION: The histological results indicated that trabeculotomy might not be an appropriate treatment for patients with atopic glaucoma, possibly because of excessive repair to the newly created uveoscleral outflow in addition to the increased postoperative fibrosis in the trabecular meshwork and Schlemm's canal.

Modified 360-degree suture trabeculotomy combined with phacoemulsification and intraocular lens implantation for glaucoma and coexisting cataract.

PURPOSE: To assess the efficacy and safety of a modified 360-degree suture trabeculotomy combined with a cataract surgery technique in patients with glaucoma and coexisting cataract. SETTING: Hokkaido University Hospital, Sapporo, Japan. DESIGN: Retrospective case series. METHODS: Medical records of patients with glaucoma having a modified 360-degree trabeculotomy combined with cataract surgery (Group 1) were reviewed. Another group of patients who had the modified 360-degree suture trabeculotomy alone served as controls (Group 2). RESULTS: Both groups comprised 46 patients. In each group, eyes were diagnosed with primary angle-closure glaucoma in 2 eyes, primary open-angle glaucoma in 24 eyes, exfoliation glaucoma in 4 eyes, uveitic glaucoma in 15 eyes, and steroid glaucoma in 1 eye. The mean preoperative intraocular pressure (IOP) values were 27.2 mm Hg ± 7.3 (SD) on 3.0 ± 0.5 medications in Group 1 and 27.7 ± 10.7 mm Hg on 2.9 ± 0.6 medications in Group 2. Twelve months after surgery, the mean IOPs were 13.4 ± 3.7 mm Hg on 0.8 ± 1.1 medications in Group 1 and 13.9 ± 4.1 mm Hg on 0.6 ± 0.9 medications in Group 2. The success rate (<18 mm Hg) at 12 months was 89.1% and 93.5%, respectively. Major complications included transient IOP spikes (30.4% and 37.0%) and prolonged hyphema (10.9% and 6.5%) in Group 1 and Group 2, respectively. CONCLUSION: The data showed the equivalent effects of suture trabeculotomy combined with cataract surgery and suture trabeculotomy surgery alone on postoperative safety and efficacy. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma.

Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies, and lowering intraocular pressure is associated with an attenuation of progressive optic nerve damage. Nevertheless, intraocular pressure (IOP) reduction alone was not enough to inhibit the progression of disease, which suggests the contribution of other factors to the glaucoma pathogenesis. In this study, we investigated the cytoprotective effect of geranylgeranylacetone (GGA) on RGCs degeneration using a normal tension glaucoma (NTG) mouse model, which lacks glutamate/aspartate transporter (GLAST) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure (IOP). Three-week-old GLAST+/- mice were given oral administration of GGA at 100, 300, or 600 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. At 5 weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. In addition, retrograde labeling technique was also used to quantify the number of RGC. Expression and localization of heat shock protein 70 (HSP70) in retinas were evaluated by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Activities of caspase-9 and -3 in retinas were also assessed. The number of RGCs of GLAST+/- mice significantly decreased, as compared to that of control mice. RGC loss was significantly suppressed by administration of GGA at 600 mg/kg/day, compared with vehicle alone. Following GGA administration, HSP70 was significantly upregulated together with reduction in the activities of caspase-9 and -3. Our studies highlight HSP70 induction in the retina is available to suppress RGC degeneration, and thus GGA may be applicable for NTG as a promising therapy.

Regulation of vascular endothelial growth factor-C by tumor necrosis factor-α in the conjunctiva and pterygium.

Vascular endothelial growth factor C (VEGF-C) plays an important role in the development of a pterygium through lymphangiogenesis. We examined the association between VEGF-C and tumor necrosis factor-α (TNF-α) in the pathogenesis of pterygia. Cultured conjunctival epithelial cells were treated with TNF-α, and the gene expression levels of VEGFC were evaluated by quantitative polymerase chain reaction (qPCR) and VEGF-C protein expression levels were measured using an enzyme-linked immunosorbent assay (ELISA). In addition, using ELISA, we evaluated the VEGF-C protein expression in the supernatants of cultured conjunctival epithelial cells, in which we neutralized TNF-α using anti­TNF-α antibody. The gene expression of tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), known as TNF receptor 1 (TNFR1), was confirmed using reverse transcription PCR in cultured conjunctival epithelial cells. Immunofluorescence microscopy was used to examine the localization of VEGF-C and TNFR1 in pterygium tissues and TNFR1 expression in cultured conjunctival epithelial cells. Immunohistochemistry was used to examine the localization of TNFR1 in pterygia and normal conjunctival tissues. VEGFC gene expression increased in cultured conjunctival epithelial cells 24 h after the addition of TNF-α. The secretion of VEGF-C protein was significantly increased 48 h after the stimulation of cultured conjunctival epithelial cells with TNF-α. Increased VEGF-C protein secretion stimulated by TNF-α was significantly reduced by anti-TNF-α neutralizing antibody treatment. In cultured conjunctival epithelial cells, TNFRSF1A and TNFR1 were expressed. TNFR1 was immunolocalized in normal conjunctival tissues and in human pterygium tissues as well as in VEGF­C­positive epithelial cells from human pterygia. Our data demonstrate that TNF-α mediates VEGF-C expression, which plays a critical role in the pathogenesis of pterygia.

Continuous Intraocular Pressure Monitoring During Nocturnal Sleep in Patients With Obstructive Sleep Apnea Syndrome.

PURPOSE: To evaluate intraocular pressure (IOP) changes during nocturnal sleep in patients with obstructive sleep apnea syndrome (OSAS) using a contact lens sensor (CLS). METHODS: This was a prospective cohort study. Seven OSAS patients who had no ocular diseases except mild cataract were enrolled. Each subject underwent CLS-based continuous IOP monitoring on one eye simultaneously with overnight polysomnography. We classified the nocturnal IOP records into nonapnea IOP and apnea IOP, according to the duration of apnea events on polysomnography within each IOP measurement time of 30 seconds every 5 minutes. RESULTS: Differences between IOP levels during nonapnea and apnea phases were statistically analyzed. The mean apnea-hypopnea index, the total number of these events per hour of sleep, was 44.2 ± 21.0, indicating the participants' severity of OSAS as moderate to severe. The mean range of IOP fluctuations during nocturnal sleep was 262.3 ± 59.5 mV eq. All patients showed lower mean IOP levels during apnea events than during nonapnea phases, with statistically significant differences detected in four of the seven patients. On average, in all seven eyes, IOP values significantly decreased by 23.1 ± 16.4 mV eq in association with apnea events. CONCLUSIONS: Obstructive apnea led to an immediate IOP decline during nocturnal sleep in patients with OSAS. Attention should be paid to IOP-independent etiology, such as episodic hypoxia, potentially linking OSAS and glaucoma.