Strengthening of the barrier function in human telomerase reverse transcription (hTERT) immortalized corneal and conjunctival epithelium by double-stranded RNA.

To investigate the response to polyinosinic:polycytidylic acid [poly(I:C)], a double-stranded RNA Toll-like receptor 3 agonist that mimics viral infection, in the barrier function of two established human telomerase reverse transcriptase-immortalized cell lines, termed HCLE for the human corneal-limbal epithelial line and HCjE for the human conjunctival-epithelial line. In this study, HCLE and HCjE cells were used to evaluate the underlying mechanism of epithelial-cell barrier function regulation. Briefly, HCLE and HCjE cells were first cultured on 12-well Transwell® (Corning®) filter-plates, and reverse transcription-polymerase chain reaction, western blotting, and immunohistochemical examinations were then performed to assess tight junction (TJ)-related protein expression and cellular distribution. Next, the barrier function of the cells was measured via transepithelial electrical resistance (TEER) and paracellular molecular flux. The cells were then stimulated with poly(I:C) and the TEER and TJ-related protein expressions were analyzed. Similar to that in in vivo epithelium, the expression of claudin (CLDN) subtypes CLDN-1, -4, and -7 was observed in the HCLE and HCjE cells, and the barrier function in the HCLE cells was tighter than that in the HCjE cells. Post stimulation with poly(I:C), TEER of the HCLE and HCjE cells increased in a dose- and time-dependent manner, the production of TJ-related protein mRNA and CLDN-4 protein were elevated, and the barrier function of the HCLE and HCjE cells increased, thus possibly indicating that the increased barrier function is a defense mechanism against viral infection.

DISTINCT CHARACTERISTICS OF SIMPLE VERSUS COMPLEX CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To compare the clinical and genetic characteristics of simple and complex central serous chorioretinopathy using central serous chorioretinopathy international group criteria. METHODS: Patients with idiopathic central serous chorioretinopathy were included. Depending on the presence or absence of retinal pigment alterations greater than 2-disc areas in either eye, patients were classified into complex or simple types. Demographic factors and clinical findings were compared between groups. CFH variants, including rs800292 and rs1329428, were genotyped using TaqMan technology. RESULTS: A total of 319 consecutive patients were evaluated at the initial presentation. Of them, 53 (16.6%) had the complex type. The complex type was exclusively seen in men (100% vs. 79.0%, P = 2.0 × 10 -4 ) and demonstrated a significantly higher proportion of bilateral involvement (75.5% vs. 17.7%, P = 6.2 × 10 -18 ) and descending tract(s) (83.0% vs. 0%, P = 1.2 × 10 -57 ) than the simple type. Increased choroidal thickness (425 ± 131 vs. 382 ± 110, P = 0.02) and decreased central retinal thickness (274 ± 151 vs. 337 ± 136, P = 2.9 × 10 -4 ) were observed for the complex versus simple type. The risk allele frequencies of both variants were significantly higher in the complex versus simple type (rs800292: 61.3% vs. 48.7%, P = 0.018; rs1329428: 65.1% vs. 54.3%, P = 0.04). CONCLUSION: In this new classification system, the complex type has distinct genetic and clinical characteristics compared with the simple type.

Progression of Myopic Maculopathy: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this study was to elucidate the risk factors for the progression of myopic maculopathy (MM) based on severity. METHODS: In this study, we conducted a systematic review and meta-analysis of the literature published before December 2020 on the risk factors for the progression of MM in patients with pathologic myopia (PM) and high myopia (HM). Odds ratios (ORs) for different stages of myopic maculopathy categorized based on the International Meta-Analysis for PM (META-PM) classification were calculated using fixed and random effects models. RESULTS: A total of 12,070 affected eyes derived from 5 cohort studies were included in the systematic review. The presence of PM at baseline was found to be significantly associated with an increased risk of MM progression (pooled ORs: 7.17, 95% confidence interval [CI]: 3.29-15.6), and the greater category of MM at baseline was found to be significantly associated with an increased risk of MM progression, that is, eyes with MM category 3 or more compared with eyes with MM category 2 (pooled OR: 10.95, 95% CI: 6.07-19.76) and eyes with MM category 4 compared with eyes with MM category 3 (pooled ORs: 2.45, 95% CI: 0.28-21.37). CONCLUSIONS: The findings in this systematic review and meta-analysis indicate that the progression of MM is associated with more severe MM at baseline.

Long-Term Benefits of Tear Exchangeable Limbal-Rigid Contact Lens Wear Therapy in Stevens-Johnson Syndrome Cases.

OBJECTIVES: To evaluate the long-term benefits of tear-exchangeable, limbal-rigid contact lens (CL) wear therapy in patients with Stevens-Johnson syndrome (SJS)-associated ocular sequelae. METHODS: This retrospective study evaluated 50 eyes of 41 SJS patients (15 men and 26 women) who underwent limbal-rigid CL wear therapy for more than 2 years post fitting. Ocular sequelae (i.e., conjunctival hyperemia, corneal neovascularization, and upper tarsus scarring) before fitting and at 3 months, 6 months, 12 months, and annually after initiating CL wear therapy were evaluated and then graded on a severity score (range: 0-3, maximum score: 3). Moreover, visual acuity (VA) at immediately post initiating CL wear therapy was evaluated. RESULTS: The mean follow-up period was 4.3±1.1 years. Compared with before fitting, the mean conjunctival hyperemia score improved from 1.14 to 0.86 at 3 months of CL wear therapy ( P <0.01) and was maintained thereafter; the mean corneal neovascularization score improved from 2.10 to 1.98 at 3 months of CL wear therapy, with no deterioration of the score observed in all cases at the final follow-up examination, and mean VA (log of minimum angle of resolution) improved from 1.60 to 1.04 at immediately post initiating CL wear therapy ( P <0.01). CONCLUSIONS: Limbal-rigid CL wear therapy can provide long-term ocular surface stabilization and improved VA in SJS patients.

Association of the CYP39A1 G204E Genetic Variant with Increased Risk of Glaucoma and Blindness in Patients with Exfoliation Syndrome.

PURPOSE: Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. DESIGN: Retrospective case study. PARTICIPANTS: A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. METHODS: Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. MAIN OUTCOME MEASURES: Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. RESULTS: The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). CONCLUSIONS: Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.

Correlation between surgical timing and postoperative ocular motility in orbital blowout fractures.

PURPOSE: The study reports the correlation between surgical timing and postoperative ocular motility in orbital blowout fractures. METHODS: This was a retrospective study of 191 patients that underwent surgical repair for unilateral orbital fractures. All patients included in the study had symptomatic diplopia from the fracture. Patients were classified into one of three groups according to the time of surgery after injury: (1) Early (within 14 days of surgery), (2) intermediate (between 15 and 30 days), and (3) late (greater than 30 days). Ocular motility was measured presurgery and at 3 and 6 months postsurgery by Hess chart with calculation of the Hess area ratio (HAR%). RESULTS: Surgery was conducted at a mean of 24.7 ± 45.0 days (range: 1-283 days) postinjury. There were 120 patients in the early surgery group (surgery at 6.8 ± 3.8 days), 38 in the intermediate surgery group (20.7 ± 4.1 days), and 33 in the late surgery group (95.1 ± 75.0 days). Overall the HAR% improved significantly from a mean of 74.2% preoperatively to 90.8% at 6 months postoperatively (p < 0.01). In the early and intermediate groups, the postoperative HAR% improved significantly with all fracture regions (orbital floor, medial wall, and combined orbital medial wall and floor) (p < 0.05). However, in the late groups, the postoperative HAR% only improved significantly with orbital floor fractures. CONCLUSION: Pre- and postoperative the HAR% give objective evidence of ocular motility improvement with early orbital floor fracture repair surgery. However, observation can be deployed, as a significant improvement in ocular motility can also be achieved with reconstructive surgery conducted 30 days or more after depressed floor-fragment fractures. Early intervention should be prioritized for symptomatic medial wall fractures, as late surgery does not improve motility.

Ex vivo Comparison of Intraocular Pressure Fluctuation during Pars Plana Vitrectomy Performed Using 25- and 27-Gauge Systems.

INTRODUCTION: The purpose of this study was to compare intraoperative intraocular pressure fluctuation using different aspiration systems and 25- and 27-gauge vitreous surgery probes. METHODS: Ex vivo, pars plana, 25- and 27-gauge vitreous surgery was performed on 4 porcine eyes, and IOP fluctuations were evaluated. We performed 3-port vitrectomy using the Constellation® Vision or the EVA® Phaco-Vitrectomy system. Each 20-s experiment was conducted 5 times for each set of conditions, each with the same substituted balanced salt solution. Real-time intraoperative intraocular pressure measurement was performed at the distal end of the infusion tube. Intraocular pressure was measured during core vitrectomy, core vitrectomy with fluid aspiration, peripheral vitreous shaving with scleral indentation, and fluid-gas exchange. The Mann-Whitney U test was used to evaluate statistical significance. RESULTS: Mean ± standard deviation intraoperative intraocular pressure fluctuation during 25- and 27-gauge core vitrectomy was 15.9 ± 1.6 and 11.9 ± 1.4 mm Hg, respectively (p < 0.05), using the Constellation system; 23.2 ± 1.4 and 14.1 ± 0.7 mm Hg, respectively (p < 0.001), using the EVA vacuum mode; and 15.0 ± 0.5 and 11.5 ± 1.4 mm Hg, respectively (p < 0.05), using the EVA flow mode. The smallest intraoperative intraocular pressure fluctuations during core vitrectomy with fluid aspiration, peripheral vitreous shaving with scleral indentation, and fluid-gas exchange were all achieved using the 27-gauge EVA flow mode; these values were 14.2 ± 0.4, 35.7 ± 0.9, and 6.4 ± 0.2 mm Hg, respectively. CONCLUSION: Regardless of the aspiration system, intraoperative intraocular pressure fluctuation was lower during 27-gauge than during 25-gauge vitrectomy. The 27-gauge EVA flow mode produced optimal intraoperative intraocular pressure stability.

Limbal-Rigid Contact Lens Wear for the Treatment of Ocular Surface Disorders: A Review.

ABSTRACT: Recently, the prescription of large-diameter rigid gas-permeable contact lenses (CLs), also known as "scleral lenses," "corneoscleral lenses," and "limbal-rigid CLs," is on the rise for the treatment of both moderate and severe ocular surface disorders (OSDs). Compared with scleral lenses, the diameter of limbal-rigid CLs is generally smaller, that is, a diameter ranging from 13.0 to 14.0 mm, and they are designed so that the peripheral edge bears on the limbus. The Suncon Kyoto-CS (Sun Contact Lens Co., Ltd.) is a novel limbal-rigid CL design with multistep curves on the peripheral edge for easy tear exchange during blinking that removes debris and prevents lens clouding or fogging, thus allowing patients to enjoy a longer daily duration of CL wear. In severe OSD cases, limbal-rigid CL wear after surgery is a noninvasive therapeutic approach that can neutralize corneal irregularities, decrease dry eye symptoms, prevent the progression or recurrence of symblepharon, and improve the patient's visual acuity and overall quality of life. Thus, surgeries such as amniotic membrane transplantation and cultivated oral mucosal epithelial transplantation, as well as limbal-rigid CL wear, which is noninvasive, are valuable and effective treatment strategies that can now be applied for the management of patients afflicted with severe OSDs.

Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy.

BACKGROUND: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density. METHODS: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×106 passaged cells were supplemented with a ROCK inhibitor (final volume, 300 µl) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 µm and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection. RESULTS: At 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 µm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98). CONCLUSIONS: Injection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534 .).

Epigenetic regulation of the epithelial mesenchymal transition induced by synergistic action of TNF-α and TGF-ß in retinal pigment epithelial cells.

To clarify the influence of tumor necrosis factor (TNF)-α on fibrotic phenotypes induced by transforming growth factor (TGF)-ß in retinal pigment epithelial cells (RPECs) by epigenetic regulation. Human primary retinal pigment epithelial cells (RPECs including ARPE19) were used in cultures in the presence or absence of TNF-α and/or TGF-ß2. RT2 Profiler™ (Qiagen) was used for PCR Array for fibrosis and epithelial mesenchymal transition (EMT). Microarray analysis by 3D gene DNA chip was outsourced to Toray Industries Inc. Quantification of histone acetyl transferase (HAT)-related and histone deacetylase (HDAC) related gene expression were also analyzed. HDAC and HAT activity was measured using an EpiQuik HDAC and HAT Activity/Inhibition Assay Kit (Epigentek). CD44, MMP-9, HAT, and HDAC in RPECs were analyzed by western blotting. Analysis of expression of the EMT/fibrosis related CD44 and MMP-9 phenotypes induced by TNF-α+TGF-ß2 revealed four alterations in RPECs: 1) abolition of TGF-ß2-induced α-SMA by TNF-α; 2) synergy between TNF-α+TGF-ß2 for induction of CD44 and MMP-9 phenotypes 3) no inhibition of HDAC activity by either TNF-α or TGF-ß2; and 4) significant inhibition of HAT activity by either TNF-α or TGF-ß2, but no synergy. The HDAC activation through HAT inhibition by TNF-α+TGF-ß was counteracted by HDAC inhibitors, leading to the inhibition of EMT/fibrosis. EMT/fibrotic CD44 and MMP-9 phenotypes were epigenetically upregulated by concerted action of TNF-α and TGF-ß in RPECs. The intervention in epigenetic regulation may hold potential in preventing intraocular proliferative diseases.

Five-Year Follow-up of First 11 Patients Undergoing Injection of Cultured Corneal Endothelial Cells for Corneal Endothelial Failure.

PURPOSE: To report the safety and efficacy of a novel cell injection therapy using cultured human corneal endothelial cells (hCECs) for endothelial failure conditions via the report of the long-term 5-year postoperative clinical data from a first-in-humans clinical trial group. DESIGN: Prospective observational study. PARTICIPANTS: This study involved 11 eyes of 11 patients with pseudophakic endothelial failure conditions who underwent hCEC injection therapy between December 2013 and December 2014. METHODS: All patients underwent follow-up examinations at 1 week, 4 weeks, 12 weeks, and 24 weeks and 1 year, 2 years, 3 years, 4 years, and 5 years after surgery. Specific corneal endothelial cell parameters (i.e., corneal endothelial cell density [ECD], coefficient of variation of area, and percentage of hexagonal cells) and central corneal thickness, best-corrected visual acuity (BCVA) on a Landolt C eye chart, and intraocular pressure (IOP) were recorded. MAIN OUTCOME MEASURES: The primary outcome was the change in central ECD after cell injection therapy, and the secondary outcome was corneal thickness, BCVA, and IOP during the 5-year-postoperative follow-up period. RESULTS: At 5 years after surgery, normal corneal endothelial function was restored in 10 of the 11 eyes, the mean ± standard deviation central corneal ECD was 1257 ± 467 cells/mm2 (range, 601-2067 cells/mm2), BCVA improved significantly in 10 treated eyes, the mean visual acuity changed from 0.876 logarithm of the minimum angle of resolution before surgery to 0.046 logarithm of the minimum angle of resolution after surgery, and no major adverse reactions directly related to the hCEC injection therapy were observed. CONCLUSIONS: The findings in this study confirmed the safety and efficacy of cultured hCEC injection therapy for up to 5 years after surgery.

CD63+ extracellular vesicles from retinal pigment epithelial cells participate in crosstalk with macrophages in the innate inflammatory axis.

The aim of the study is to clarify the participation of extracellular vesicles (EV) secreted by murine primary retinal pigment epithelial (mpRPE) cells in the cell to cell communication with macrophages (Mps), firstly described by the authors in 2016. In ocular inflammation, Mps act as sources of tumor necrosis factor-α (TNF-α), an activator of RPE cells. TNF-α stimulates the production of monocyte chemotactic protein (MCP-1) by RPE cells, thereby causing greater recruitment of Mps to the sub-RPE space. Murine RAW 264.7 Mps cells were co-cultured with C57BL/6 mouse mpRPE cells, either together or separated in transwells, vertically or horizontally connectable, with 0.40 or 0.03 µm membrane filters. The association of EV with mpRPE or RAW 264.7 was quantified by fluorescence cell sorting (FACS) using Qdot655 streptavidin-conjugated biotinylated EV. Increased levels of CD63+ EV were detected in co-cultures by western blotting or FACS analysis, in accordance with the increased production of nanoparticles (50-150 nm) detected by Nanosight tracking analysis. The gene expressions of cytokines, MCP-1, IL-6, IL-8, and VEGF in mpRPE cells and the corresponding proteins were increased in co-cultures even in transwells, vertically connected with 0.40 µm membrane filters, while the repressed TNF-α protein production was not affected. Most of the CD63+ EVs produced by mpRPE cells in co-cultures were associated with Raw264.7, but not with mpRPE cells. Semi-purified CD63+ EV secreted from mpRPE cells, increased the secretion of MCP-1, IL-6, and VEGF in co-cultures with RAW 264.7. Culture chamber separation horizontally connected with 0.03 µm membrane filters reduced this increased secretion. Collectively, mpRPE derived CD63+ EV partly participate in the sub-retinal innate inflammation. To evaluate the functional damage of RPE cells upon chronic exposure to here defined EVs will be the critical issue to uncover their roles in chronic retinal degenerative diseases.

Mitochondrial miRNA494-3p in extracellular vesicles participates in cellular interplay of iPS-Derived human retinal pigment epithelium with macrophages.

To explore new molecular targets for therapy in human model systems by discerning the role of extracellular vesicle (EV) microRNAs (miRs) secreted by human retinal pigment epithelium (hRPE) cells and their cellular interplay with macrophages (Mps). Human Mps differentiated from THP-1 cells stimulated by phorbol myristate acetate were co-cultured with induced pluripotent stem cell-derived differentiated hRPE (iPS-hRPE) cells in Transwell® system separated by 0.40 µm or 0.03 µm filters. EV-associated CD63+ proteins (CD63+ EV) were detected by western blotting, and secreted EVs were analyzed by Nanosight tracking. The miR profiles of the secreted EVs were determined using 3D-gene human microRNA chips (Toray Industries, Inc.). Levels of CD63+ EV were increased in co-cultures concomitantly with the increased production of EV particles (50-150 nm). The increased production of EVs was associated with higher production of MCP-1, IL-6, IL-8 from hRPE cells, and VEGF and repressed production of TNF-α from Mps and pigment epithelium-derived factor (PEDF) from RPE cells. Ultracentrifugation of semi-purified EVs increased the secretion of these pro-inflammatory cytokines and EV particles from hRPE cells, but this effect was eliminated in transwells equipped with 0.03 µm filters, whereas no repression of PEDF and TNF-α secretion occurred. 3D-gene miR analysis revealed a selective increase in secretion of miR494-3p in EVs from iPS-hRPE cells during the interplay with Mps. The miRs in EVs secreted by hRPE cells may have a critical role in the vicious inflammatory cycle, whereas repression of TNF-α and PEDF require cell-to-cell contact that is independent of EVs or exosomes. MiR494-3p may be a candidate molecular target of diagnosis and therapy for age-related macular degeneration.

Assessment of a Consecutive Series of Orbital Floor Fracture Repairs With the Hess Area Ratio and the Use of Unsintered Hydroxyapatite Particles/Poly l-Lactide Composite Sheets for Orbital Fracture Reconstruction.

PURPOSE: The purpose of this study is to report the outcomes of a series of orbital fracture repairs, their assessment with the Hess area ratio (HAR%), and the use of unsintered hydroxyapatite (HA) implants for reconstruction. METHODS: This study involved 207 consecutive unilateral orbital fractures with symptomatic diplopia that underwent surgical repair within 28 days of injury. Ocular movement was measured presurgery and at 3 and 6 months postsurgery by Hess chart with calculation of the HAR%. RESULTS: Surgery was conducted on 207 patients (161 males and 46 females; mean age, 27.8 years) at a mean of 9.9 days postinjury and with a mean follow-up of 8.6 months. There were 160 patients with orbital floor fractures, 27 with medial wall fractures, and 20 with combined orbital medial wall and floor fractures, 135 of 207 patients had orbital blowout fractures, and 72 had orbital trap-door fractures. The HAR% improved significantly from a mean of 73.8% preoperatively to 92.7% postoperatively (P < .01). Orbital fractures were reconstructed with either unsintered HA particles/poly l-lactide composite sheet (133 patients), a silicone silastic sheet (47 patients), a combination of sheets (15 patients), or without an implant (12 patients). There was no significant difference in the HAR% improvement between the different implants. CONCLUSIONS: Very good outcomes can be achieved with early orbital floor fracture repair surgery, which can be assessed preoperatively and postoperatively by HAR%. Unsintered HA/poly l-lactide composite sheets are an effective absorbable material for orbital floor fracture reconstruction.

The Challenge of Contact Lens Visual Rehabilitation for Open Globe Injuries in Children Under 5 Years of Age.

PURPOSE: To investigate the clinical course of children younger than 5 years old who underwent rigid gas-permeable (RGP) contact lens (CL) wearing as visual rehabilitation of open globe injuries (OGIs) in Japan. METHODS: This retrospective case series involved six eyes of six children (four boys and two girls) with OGIs. The mean patient age at injury was 4.0±0.83 SD (range: 2.5-5 years), and the mean follow-up period was 42.9 months (range: 31.6-52.8 months). In each child, data regarding injury type, ocular surgery performed, outcomes of amblyopia management (including best-corrected visual acuity [BCVA] with RGP CL or spectacles), the RGP CL-wear training period, and rate of continuous RGP CL-wear were analyzed. RESULTS: Trauma type was penetrating injury (four eyes) and globe rupture (two eyes). All six cases showed lens penetration, and underwent corneal suture, lensectomy, and pars plana vitrectomy under general anesthesia. The mean RGP CL-wear training period was 3.5 months, and only one of the six cases discontinued RGP CL use. The mean BCVA with spectacles and with RGP CL was LogMAR: 1.52±0.41 (range 1.00-2.00) and 0.73±0.41 (range: 0.30-1.15), respectively. In all patients, except in one case in which strabismus developed, BCVA improved with RGP CL wear more than 0.2 logMAR compared with that with spectacles. CONCLUSION: Although the training period for RGP CL-wear is long in pediatric patients with OGIs, the treatment can be effective for refractive problems and for preventing the development of strabismus.

Outcomes of combined gonioscopy-assisted transluminal trabeculotomy and goniosynechialysis in primary angle closure: a retrospective case series.

PURPOSE: To evaluate the additional intraocular pressure (IOP) lowering effect of gonioscopy-assisted transluminal trabeculotomy (GATT) to contemporary goniosynechialysis (GSL) in endeavouring to abolish subsequent occlusion after chronic iridotrabecular contact in primary angle closure (PAC) patients. METHODS: A retrospective case series of all PAC eyes underwent GATT + GSL with or without phacoemulsification and intraocular lens implantation (PEA + IOL) from December 2016 to May 2018 were recruited. IOP and the number of anti-glaucoma medications were compared pre- and post-operatively by Wilcoxon signed-rank test. Repeated measure ANOVA was used to evaluate the difference in IOP change after the operation between a subgroup of operations (GATT + GSL + PEA + IOL and GATT + GSL) and the arc of cutting of trabeculotomy. RESULTS: Thirty-nine eyes of 30 patients, 37 chronic angle closure glaucoma (CACG), 1 acute primary angle closure (APAC), and 1 plateau iris syndrome were recruited. Mean preoperative IOP was 21.8 ± 5.4 mmHg. Mean post-operative IOP was lowered to 15.1 ± 3.8 mmHg at 1 month, 14.4 ± 1.2 mmHg at 3 months, 14.8 ± 2.1 mmHg at 6 months, 14.5 ± 0.8 mmHg at 1 year, and 15 at 2 years (P < 0.001, P = 0.0012, P = 0.001, P = 0.028, and P = 0.317 (n = 1), consecutively). Mean of overall post-operative IOP at the last follow-up was 15.1 ± 4.4 mmHg (P < 0.001). Mean preoperative number of anti-glaucoma medications was 3.5 ± 1.4. Mean post-operative number of anti-glaucoma medications was reduced to 1.5 ± 1.4 at 1 month, 0.9 ± 0.9 at 3 months, 1.4 ± 1.4 at 6 months, 1.5 ± 0.5 at 1 year, and 2 at 2 years (P < 0.001, P = 0.01, P = 0.002, P = 0.028, and P = 0.317 (n = 1), respectively). Mean of overall post-operative number of anti-glaucoma medications was 1.1 ± 1.2 (P < 0.001). There was no significant difference found between the IOP lowering effect in subgroup analysis. CONCLUSION: GATT + GSL could significantly reduce IOP and number of anti-glaucoma medications from baseline compared to the last follow-up; however, there seemed not to be any superiority to the effects found in previous studies reported about GSL + PEA or PEA alone in PAC patients.

Evaluation of pre- and post-surgery reading ability in patients with epiretinal membrane: a prospective observational study.

BACKGROUND: This study aimed to investigate the pre- and post-surgery reading ability in patients with idiopathic epiretinal membrane (ERM) to evaluate whether measurement of reading performance is a helpful test in addition to visual acuity (VA) as an assessment measure. METHODS: This prospective observational study involved 42 eyes of 40 patients with idiopathic ERM. Best-corrected visual acuity (BCVA), reading ability, and metamorphopsia score were evaluated at baseline and at 3, 6, and 12 months post-surgery. As the outcome measure, the reading ability of each patient (i.e., overall performance) was examined with MNREAD-J, the Japanese version of the MNREAD reading acuity (RA) charts, to determine RA, critical print size (CPS), and maximum reading speed (MRS). Generally, a difference of 0.2 logMAR or more is considered a significant change in BCVA. Thus, as a subgroup analysis, we additionally evaluated the BCVA and reading ability of the patients with a BCVA difference of 0.1 logMAR or less between at baseline and at 12 months post-surgery. RESULTS: Relative to their values at baseline, the subjects exhibited significantly improved BCVA, RA, and CPS throughout the post-surgery examination period (P < 0.001) and significantly improved MRS at 12 months post-surgery (P = 0.04). No significant change in the vertical metamorphopsia score was observed throughout the post-surgery follow-up period. However, and compared to the value at baseline, significant improvements in the horizontal metamorphopsia score were observed at 3, 6 (P < 0.05), and 12 months (P < 0.001) post-surgery. In the subgroup analysis of the 23 eyes that exhibited a BCVA improvement of 0.1 logMAR or less, the median BCVA did not change, but the median RA and CPS improved by 0.2 logMAR. CONCLUSIONS: Our findings showed that the surgical removal of ERM improves reading ability, even when the BCVA score does not improve. The measurement of reading performance appears to be a helpful test in addition to VA as a measure for assessing the surgical removal of ERM.

pH balance and lactic acid increase in the vitreous body of diabetes mellitus patients.

Although there have been no previous reports on the pH of the human vitreous body, it has been highly theorized that it changes in patients with diabetes mellitus (DM). In humans, it is necessary to measure the vitreous pH in vitro, which is an important point that presents a major problem, as vitreous pH immediately changes when exposed to air. The purpose of this present study was to report our recent development of an in vitro method for measuring vitreous pH via the combination of 27-gauge (G) vitreous surgery and a blood gas analyzer, as well as our investigative findings on whether or not there is a difference of pH depending on the presence of diabetes mellitus (DM). This cross-sectional study involved 30 subjects [18 subjects without DM (DM-) and 12 subjects with DM (DM+)] with no previous history of ophthalmologic surgery. The DM+ group included 6 cases of proliferative diabetic retinopathy (PDR) and 6 cases of non-PDR (NPDR). The DM- Group was comprised of patients with a macular hole or idiopathic epiretinal membrane. The DM+ Group included patients not only with macular hole or idiopathic epiretinal membrane but also diabetic macular edema, however, patients with obvious vitreous hemorrhage were excluded. In all patients, a vitreous specimen was anaerobically obtained at the start of 27G pars plana vitrectomy, with a venous blood sample being collected immediately prior to surgery. Between the DM- and DM+ subjects, pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), K+, Na+, Ca2+, Cl-, lactate, and glucose were compared. In the items in which a significant difference was found between DM- and DM+, the values between the PDR and NPDR cases were also compared. Our findings showed no significant difference in vitreous and venous-blood pH between the DM- and DM+ subjects. The vitreous biochemical data revealed that Ca2+ significantly reduced and lactate and glucose significantly increased in DM+ compared to DM-. Thus, we compared Ca2+, lactate, and glucose between the PDR and NPDR cases. Although glucose did not significantly change, Ca2+ significantly decreased and lactate significantly increased in the PDR cases. The venous biochemical data revealed that only glucose significantly increased in DM+. The data in all investigated items was found to be significantly different between the vitreous and venous samples. Our findings revealed that lactate increases and Ca2+ decreases in the vitreous body of DM patients, especially those with PDR, probably due to the increased production of lactic acid. However, although the production of lactic acid increased, the pH remained at a nearly constant value, thus suggesting that the human vitreous body has a high buffering capacity.

Multicenter survey of sutureless 27-gauge vitrectomy for primary rhegmatogenous retinal detachment: a consecutive series of 410 cases.

PURPOSE: To evaluate the surgical outcomes of the 27-gauge (G) vitrectomy system for the treatment of primary rhegmatogenous retinal detachment (RRD). METHODS: This retrospective consecutive series multicenter study involved a total of 410 eyes of 406 patients who underwent 3-port transconjunctival 27G pars plana vitrectomy (PPV) for RRD between November 2014 and December 2016 and who were followed for a minimum of 3 months postoperative. The main outcome measure was primary reattachment, with the secondary outcome measures being final reattachment, improvement of visual acuity (VA), intraocular pressure (IOP), intraoperative and postoperative complications, and surgery time. RESULTS: Of the 410 treated eyes, primary reattachment was achieved in 392 (95.6%) and final reattachment was achieved in 410 (100%). In 226 eyes (55.1%) with macula-on RRD, the mean logarithm of the minimum angle of resolution (logMAR) VA improved from 0.16 ± 0.51 pre-surgery to 0.02 ± 0.14 post-surgery (P = 0.11). In 184 eyes (44.9%) with macula-off RRD, logMAR VA improved from 1.06 ± 0.77 pre-surgery to 0.26 ± 0.35 post-surgery (P < 0.001). Following surgery, the mean IOP was highest at 1 day (15.7 ± 7.0 mmHg) postoperative. In all eyes, surgery was concluded without the use of sutures or the need of conversion to a larger-gauge instrument. Although hypotony was observed in 14 (3.4%) of the 410 treated eyes at 1 day postoperative, it spontaneously resolved within 1 week without additional surgical intervention. No postoperative complications such as infectious endophthalmitis were observed throughout the follow-up period. CONCLUSION: Our findings show that 27G PPV is both safe and effective for the treatment of primary RRD.