Effect of Tauroursodeoxycholic Acid on Inflammation after Ocular Alkali Burn.

Inflammation is the main cause of corneal and retinal damage in an ocular alkali burn (OAB). The aim of this study was to investigate the effect of tauroursodeoxycholic acid (TUDCA) on ocular inflammation in a mouse model of an OAB. An OAB was induced in C57BL/6j mouse corneas by using 1 M NaOH. TUDCA (400 mg/kg) or PBS was injected intraperitoneally (IP) once a day for 3 days prior to establishing the OAB model. A single injection of Infliximab (6.25 mg/kg) was administered IP immediately after the OAB. The TUDCA suppressed the infiltration of the CD45-positive cells and decreased the mRNA and protein levels of the upregulated TNF-α and IL-1ß in the cornea and retina of the OAB. Furthermore, the TUDCA treatment inhibited the retinal glial activation after an OAB. The TUDCA treatment not only ameliorated CNV and promoted corneal re-epithelization but also attenuated the RGC apoptosis and preserved the retinal structure after the OAB. Finally, the TUDCA reduced the expression of the endoplasmic reticulum (ER) stress molecules, IRE1, GRP78 and CHOP, in the retinal tissues of the OAB mice. The present study demonstrated that the TUDCA inhibits ocular inflammation and protects the cornea and retina from injury in an OAB mouse model. These results provide a potential therapeutic intervention for the treatment of an OAB.

Inhibition of endoplasmic reticulum stress by 4-phenylbutyrate alleviates retinal inflammation and the apoptosis of retinal ganglion cells after ocular alkali burn in mice.

OBJECTIVE: Retinal ganglion cell (RGC) apoptosis is one of the most severe complications that causes permanent visual impairment following ocular alkali burn (OAB). Currently, very few treatment options exist for this condition. This study was conducted to determine the effect of 4-phenylbutyric acid (4-PBA) on endoplasmic reticulum (ER) stress after OAB using a well-established OAB mouse model. METHODS: Ocular alkali burn was induced in C57BL/6 mouse corneas using 1 M NaOH. 4-PBA (10 mg/kg; 250 µL per injection) or saline (250 µL per injection) was injected intraperitoneally once per day for 3 days before the establishment of the OAB model. The apoptosis of retinal ganglion cells (RGCs) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the histological damage was examined by hematoxylin and eosin and immunofluorescence assay on retinal flat mounts. The key inflammatory response and the expression of ER stress-related markers in the retinal tissues were assessed by real-time PCR, western blotting and histologic analyses. RESULTS: 4-PBA significantly alleviated the apoptosis of RGCs and prevented the structural damage of the retina, as determined by the evaluation of RGC density and retinal thickness. Inhibition of ER stress by 4-PBA decreased the expression of vital proinflammatory cytokines, tumor necrosis factor alpha, and interleukin-1 beta; and suppressed the activation of retinal microglial cells and nuclear factor-kappa B (NF-κB). 4-PBA reduced the expression of the ER stress molecules, glucose-regulated protein 78, activated transcription factor 6, inositol-requiring enzyme-1 (IRE1), X-box-binding protein 1 splicing, and CCAAT/enhancer-binding protein homologous protein, in the retinal tissues and RGCs of OAB mice. CONCLUSIONS: The present study demonstrated that the inhibition of ER stress by 4-PBA alleviates the inflammatory response via the IRE1/NF-κB signaling pathway and protects the retina and RGCs from injury in an OAB mouse model. Such findings further suggest that 4-PBA might have potential therapeutic implications for OAB treatment.

Clinical Features of Endogenous Endophthalmitis Secondary to Minimally Invasive Upper Urinary Tract Calculus Removal.

PURPOSE: To evaluate endogenous endophthalmitis clinical features following minimally invasive removal of upper urinary tract calculi. METHODS: Medical records of twelve patients (17 eyes) with endogenous endophthalmitis secondary to minimally invasive upper urinary tract calculus removal were retrospectively reviewed. RESULTS: Diabetes mellitus was found in 7 patients (58%). 10 patients (83%) suffered from fever. The stone extraction and ocular symptom onset interval ranged from 2 to 22 days. All eyes presented as vitritis and fluffy yellow-white retinal exudates. Hypopyon was only found in 3 eyes (18%). 5 patients (42%) were misdiagnosed as uveitis which led to mismanagement. Ocular fluids were culture positive for only C. albicans in 12 eyes (71%). 10 of 12 eyes (83%) with silicon oil tamponade obtained a final BCVA≥0.05. CONCLUSIONS: C. albicans was the most common endogenous endophthalmitis pathogen after urinary calculus removal by minimally invasive surgery. Pars plana vitrectomy with silicon oil tamponade may be helpful to achieve a favorable visual outcome. Routine ophthalmologic evaluation by the uveitis or vitreoretinal specialist may be necessary within 2 weeks after the urological procedures.

Changing Trends in Firework-Related Eye Injuries in Southern China: A 5-Year Retrospective Study of 468 Cases.

Firework-related eye injury is a horrible medical problem and creates huge health and social burdens. Herein, we explored the changing trends and demographic and clinical features of firework-related eye injury, in an effort to inform strategies to prevent this injury. We reviewed the data of 468 hospitalized patients who underwent surgery for firework-related eye injury at the Zhongshan Ophthalmic Center between January 2013 and December 2017. During this period, the trend in firework-related eye injuries was stable (mean, 93 ± 14 cases per year), and fireworks were the major cause of explosive eye injury. The average age of the patients was 24 ± 18 years and 87% of the patients were male, with boys under 10 years of age comprising the largest group (27% of patients). There were an average of 24 ± 7 cases per year from urban areas and 70 ± 8 cases from rural areas (P < 0.05). Furthermore, 21 ± 5% of cases occurred during Spring Festival. After treatment, the best corrected visual acuity was increased compared to that before treatment, and the intraocular pressure tended to become normal by the final visit (P < 0.05). The top three diagnoses were cataract (39%), retinal detachment (18%), and choroidal detachment (14%). Additionally, the most common surgery was cataract extraction (25%), followed by pars plana vitrectomy (19%) and pars plana vitrectomy plus pars plana lensectomy (10%). Over the five-year study period, day surgery hospitalization increased from 1% to 32%. This was associated with a corresponding decrease in the length of hospitalization, without adverse events, demonstrating that day surgery is feasible in firework-related eye injury cases. The present study results suggest that greater attention should be paid to firework-related eye injury, and a variety of measures should be taken to prevent this kind of ocular tragedy.

Risk Factors Associated with Failure of Direct Cyclopexy in the Treatment of Small to Moderate Tramatic Cyclodialysis Clefts.

BACKGROUND: To evaluate the risk factors associated with failure to correct hypotony using direct cyclopexy in patients with traumatic cyclodialysis cleft. METHODS: In a series of 116 patients with traumatic cyclodialysis who underwent direct cyclopexy at Zhongshan Ophthalmic Center from January 2008 to August 2018, the clinical correlation between the risk factors and failure of the operation were retrospectively studied, after adjusting for other potential confounders. RESULTS: The curative ratio after one procedure was 82.76%, whereas 20 (17.24%) eyes experienced treatment failure after the first surgery. The degree of anterior chamber angle closure was significantly wider in patients with a failed first surgery than in patients for whom one procedure was a success (p = .046). The risk of failure to achieve closure increased as the angle-closure exceeded 5 clock hour (odds ratio, 10.39; 95% confidence interval, 1.75-61.72; p = .010). An analysis of the recurrent position indicated that an angle closure exceeding 5 clock hour may impede accurate cleft location and is thus associated with an increased risk of failure to correct hypotony. CONCLUSION: Exceeding the threshold of 5 clock hour in anterior chamber angle closure may impede accurate cleft location and, thus, present a higher risk of failure to correct hypotony using direct cyclopexy. These patients may need injection of a viscoelastic agent into the anterior chamber by paracentesis to deepen the anterior chamber and to delineate the clefts using gonioscopy pre- or intraoperatively.

Effect of vitrectomy with intrasurgical regulation of intraocular pressure in a rabbit model of central retinal artery occlusion.

Central retinal artery occlusion (CRAO) is an ophthalmic emergency that causes severe and permanent visual impairment. The effects of conventional treatments on recanalizing retinal arteries and improving visual outcome are equivocal. This study was designed to determine the possible benefits of pars plana vitrectomy (PPV) with intrasurgical regulation of intraocular pressure using intraocular vascular counterpulsation (IVT). CRAO was induced by 532-nm argon green laser activation of auricular intravenous injected rose bengal, a photosensitive dye, in the central retinal arteries (CRA) of eighty-four New Zealand white albino rabbits. CRAO rabbits were randomly assigned to photocoagulation, vitrectomy and counterpulsation groups. Depending on the time intervals between surgery and CRAO induction, vitrectomy and counterpulsation groups were further divided into 2 h (2h), 6 h (6h) and 24 h (24h) subgroups. The proportion of eyes with complete recanalization was significantly higher in the 2h counterpulsation subgroup after three days (P = 0.032) and in all counterpulsation subgroups after one week (P = 0.020). After one month, the 2h and 6h counterpulsation subgroups showed greater oscillatory potential (OPs) responses (F = 3.519, P = 0.049). The 2h counterpulsation subgroup also exhibited greater b-wave amplitude in photopic 3.0 Flicker(F = 4.530, P = 0.044). Histologic evaluation revealed less destruction in the inner retina for the 2h and 6h counterpulsation subgroups. Expression of HSP70 was higher in the 2h and 6h counterpulsation subgroups (F = 48.915,P < 0.001). Levels of HSP90 were lower in all counterpulsation subgroups (F = 30.065,P < 0.001). Levels of TNF-α were lower in the 2h counterpulsation subgroup (F = 14.762,P < 0.001). These results indicate that PPV with IVT was effective to recanalize retinal arteries after CRAO. Early intervention provided better morphologic and functional prognosis for inner retina. The protective effect was related with higher retinal levels of HSP70 and lower levels of HSP90 and TNF-α.

The anti-inflammatory effect of minocycline on endotoxin-induced uveitis and retinal inflammation in rats.

Purpose: Uveitis is a serious inflammatory disease of the uvea, frequently leading to visual impairment and irreversible blindness. Here, we investigated the anti-inflammatory effect of minocycline on rat endotoxin-induced uveitis (EIU) and retinal inflammation. Methods: For in vivo studies, the rat EIU model was induced with intravitreal injection of lipopolysaccharide (LPS). Minocycline was administered intraperitoneally 2 h before and after the LPS injection. The severity of the ocular inflammation was evaluated with slit-lamp photography, aqueous humor cell counting, protein quantitative determination, and histological analysis. Retinal microglia were labeled with a fluorescent dye 4Di-10ASP. Microglial activity and inflammatory cytokine production were analyzed with immunofluorescence and real-time PCR. For the in vitro studies, BV-2 microglia cells were stimulated with LPS or cotreated with minocycline for 6 h. Toll-like receptor (TLR) 2/4 levels were determined with real-time PCR and western blotting. Results: The LPS-challenged eyes displayed severe inflammation in all ocular structures, including a large number of anterior chamber cells, fibrin exudation, hypopyon, and infiltrated inflammatory cells in the vitreous and retina. Immunostaining of the retinal whole-mounts also revealed numerous retinal microglia were activated promptly, and then more and more peripheral leukocytes were recruited and infiltrated in the LPS-injected retinas. Additionally, the production of tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand 2 (CCL-2), interleukin-1 beta (IL-1ß), and IL-6 was dramatically increased. However, minocycline treatment strongly inhibited microglia activation, decreased inflammatory cytokine production, prevented peripheral inflammatory cell recruitment, and significantly attenuated ocular inflammation. Finally, we demonstrated the mechanism of the microglia inactivation effect of minocycline is via suppression of TLR4 signaling. Conclusions: This study indicates minocycline is far beyond an antibiotic. It not only attenuates rat EIU but also inhibits retinal inflammation through inactivating microglia, inhibiting inflammatory cell recruitment and inflammatory cytokine production.

Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis.

Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin­induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS­induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick­end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription­quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC­1 and ICAM­1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels and downregulated Mcl­1 expression levels were observed. In conclusion, roscovitine ameliorates EIU by effecting neutrophil apoptosis. Timely apoptosis of neutrophils may be an effective process to promote the amelioration of EIU.

Radial Retinotomies with Endodiathermy for Severe Proliferative Vitreoretinopathy: Short-Term Results.

Purpose. Retinal redetachment of silicone oil-filled eyes continues to be a frustrating condition that typically requires retinectomy. We proposed radial retinotomy as a potentially less invasive surgery. Here, we preliminarily explored its feasibility, efficacy, and safety. Methods. Totally 9 eyes of 9 consecutive patients were included in a prospective noncomparative trial. A series of retinotomies were created by endodiathermy in a radial pattern to relax the foreshortened retina. The eye was refilled with fresh silicone oil. The treated eyes were examined via visual acuity (VA) tests, tonometry, slit-lamp microscopy, and fundus photography during a 6-month observation period. Results. The procedure was completed in an average of 28 minutes from silicone oil removal to fresh silicone oil placement. Fundus photography demonstrated that 7 of the 9 eyes (78%) exhibited retinal reattachment. On average, VA was significantly improved within the first 2 weeks (P = 0.02) and remained stable for the following 6 months. The change in intraocular pressure was not significant (P = 0.76), and no adverse event was observed (0%). Conclusion. Radial retinotomies with endodiathermy were shown to be feasible, effective, and safe in selected cases of inferior contracted retina without vitreous base fibrosis over a 6-month observation period. This trial is registered with NCT02201706.

The Changes of Retinal Saturation after Long-Term Tamponade with Silicone Oil.

PURPOSE: To evaluate the effects of long-term tamponade with silicone oil on retinal saturation. METHODS: A total of 49 eyes that received tamponade with silicone oil were included. The patients were divided into 3 groups (3-6 months, 6-9 months, and >9 months) according to the duration of silicone oil tamponade. Retinal oximetry was performed using the Oxymap system before and 2 months after silicone oil removal. RESULTS: The mean retinal oxygen saturation before silicone oil removal was 107% ± 12% in the arterioles and 60% ± 10% in the venules, with an overall arteriovenous difference (AVD) of 47% ± 14%. The AVD in the >9-month group was significantly higher than that in the 3-6-month group (54% ± 16% versus 44% ± 11%, P = 0.042). After silicone oil removal, the AVD in the >9-month group was significantly decreased (45% ± 9% versus 54% ± 16%, P = 0.009); additionally, the arterioles were significantly wider than before surgery (10.8 ± 0.7 pixels versus 10.4 ± 0.9 pixels, P = 0.015). CONCLUSIONS: The tamponade with silicone oil for more than 9 months will cause the alterations of retinal saturation and the narrowing of retinal arterioles, which may further interfere with the oxygen metabolism in the retina.

Residual lens cortex material: potential risk factor for endophthalmitis after phacoemulsification cataract surgery.

PURPOSE: To evaluate the bacterial growth potential of residual lens cortex after phacoemulsification with the development of endophthalmitis. SETTING: University medical center. DESIGN: Experimental study. METHOD: Staphylococcus aureus and Staphylococcus epidermidis were dispensed into aqueous humor or serial dilutions of lens cortex that were obtained from cataract patients during phacoemulsification. After a 24-hour incubation, the colony-forming unit (CFU) was quantified. Eighty rabbits had phacoemulsification. Complete lens cortex removal was performed in 40 rabbits, while a quarter of lens cortex was retained in 40 rabbits. Staphylococcus aureus, with an inoculum size of 32 CFU, 56.3 CFU, and 108.6 CFU, was injected intracamerally at the conclusion of surgery and the production of endophthalmitis was measured 72 h later. The aqueous and vitreous humor samples were collected for microbiological diagnosis. RESULTS: The increase in bacterial growth of S aureus and S epidermidis was statistically significantly greater in each dilution of lens cortex than in aqueous humor (P < .001, Student t test). With inoculum of 32.0 CFU or 56.3 CFU of S aureus, there was a statistically higher incidence of bacterial culture-proven endophthalmitis in the residual lens cortex eye group than in the normal aphakic eye group (P < .05, Fisher exact test). CONCLUSIONS: Lens cortex was associated with a significant increase in bacterial growth compared with aqueous humor. Therefore, eyes with residual lens cortex seem more prone to develop endophthalmitis if anterior chamber bacterial contamination occurs during phacoemulsification. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

[Effects of Staphylococcus aureus supernatant on expression of various cytokines by neutrophils and retinal pigment epithelium cells].

OBJECTIVE: To evaluate the effects of Staphylococcus aureus supernatant on the levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in co-cultures of neutrophils and retinal pigment epithelium (RPE) cells. METHODS: The co-culture system was established by co-culturing of human RPE cell line D407 and human peripheral blood neutrophils. Bacterium-free supernatant of Staphylococcus aureus ATCC29213 was added to the co-culture system for studying its effects. The volume of bacterium-free supernatant was divided into six groups: negative control, brain-heart infusion control, 50 µl, 100 µl, 250 µl and 500 µl group. The number of neutrophils was divided into four groups: negative control, 1 × 10(4), 5 × 10(4) and 5 × 10(5) group. The supernatants was collected at 6 h, 12 h, 24 h, 48 h and 72 h later and the levels of IL-1ß, TNF-α and IL-6 were measured by ELISA kits. RESULTS: When RPE cells were cultured with different doses of bacterium-free supernatant (0, 50, 100, 250 and 500 µl), the levels of IL-1ß was positively correlated with the volume of bacterium-free supernatant and the duration. The levels of IL-6 were significantly higher than that of the control group in the 500 µl group at 24 h [(23.17 ± 3.16) ng/L vs (7.61 ± 1.53) ng/L] and 48 h [(35.00 ± 4.37) ng/L vs (13.17 ± 3.27) ng/L] duration (P = 0.001 and P = 0.026, respectively). When RPE cells were co-cultured with the bacterium-free supernatant and the neutrophils (1 × 10(4), 5 × 10(4) and 5 × 10(5) cells) for 6 and 12 h, the levels of IL-1ß in the 5 × 10(5) group at both 6 h [(236.62 ± 8.20) ng/L] and 12 h [(447.42 ± 35.13) ng/L] was statistically higher than that in other groups (6 h: P = 0.000, P = 0.000, P = 0.002; 12 h: P = 0.000, P = 0.000, P = 0.000, respectively). The levels of IL-6 in the 5 × 10(5) group [(46.96 ± 2.72) ng/L] was significantly higher than that in the other groups at 12 h (P = 0.000, P = 0.000, P = 0.000, respectively). TNF-α could not be detected in the conditioned media from all cultures. CONCLUSIONS: Both IL-1ß and IL-6 are expressed in the co-cultures of neutrophils and RPE cells with Staphylococcus aureus supernatant. IL-1ß is upregulated at the early stage and the high level is maintained longer than that of IL-6. The virulence factor of bacteria and the neutrophil may play a role in the expression of IL-1ß and IL-6 in the RPE cells.