SPONTANEOUS CLOSURE OF MYOPIC MACULAR HOLE TWICE WITHOUT POSTERIOR VITREOUS DETACHMENT.

PURPOSE: To present a case of a myopic macular hole that spontaneously closed twice in the presence of a broadly adherent posterior hyaloid membrane. METHODS: Case report. RESULTS: A 49-year-old man with high myopia and pseudophakia had a full-thickness macular hole in the left eye. The hole spontaneously closed in all retinal layers before the elective surgery, but the macular hole recurred one month later. The hole started sealing again spontaneously after one month, leaving a defect in the outer retinal layers. Four months later, the outer layer defect sealed and a lamellar macular hole developed. Throughout the course, the posterior hyaloid membrane remained parallel to the macular surface. The macular morphology and the patient's vision remained stationary at the 2-year follow-up. CONCLUSION: This case demonstrated that myopic macular holes can form and seal repeatedly with a broadly adherent posterior hyaloid membrane. Although bridging phenomenon was the common sign indicating the initiation of the two hole closures, different patterns of tissue regeneration ensued.

Sex-related differences on the risks of in-hospital and late outcomes after acute aortic dissection: A nationwide population-based cohort study.

OBJECTIVE: The aim of this study is to evaluate the sex-related differences on the risks of perioperative and late outcomes for adult acute aortic dissection (AAD) patients following surgical management. METHODS AND RESULTS: By using Taiwan National Health Insurance Research Database, totally 1,410 female and 3,432 male patients were identified to first-ever receive type A AAD open surgery or type B AAD stenting treatment from 2004 to 2013. We assessed the sex-related difference on outcomes, including in-hospital mortality, all-cause mortality, aortic death, redo aortic surgery, ischemic stroke, and depression during the follow-up period. The analysis was done separately for type A and type B surgeries. RESULTS: On average, female patients diagnosed with AAD were older than males. There was no significant sex difference of in-hospital mortality or all-cause mortality for both type A open and type B stent surgeries. The risk of redo aortic surgery was significantly greater in males than females (7.8% vs. 4%; unadjusted subdistribution hazard ratio [SHR] 0.51, 95% CI 0.38-0.69) for type A open surgery, but not for type B stent surgery. Noticeably, the risk of newly-diagnosed depression was significantly greater in females than males (8% vs. 5.1%; unadjusted SHR 1.6, 95% CI 1.24-2.06) for type A open surgery, but not for type B stent surgery. CONCLUSIONS: No significant sex-related difference was found for the in-hospital mortality or accumulative all-cause mortality. However, there were more redo aortic surgeries for males and more postoperative depression for females in type A AAD population.

Clinical Manifestations and Implications of Nonneoplastic Uveitis Masquerade Syndrome.

PURPOSE: To investigate the clinical manifestations and systemic and ocular implications of nonneoplastic uveitis masquerade syndrome (NNUMS). DESIGN: Retrospective case series. METHODS: The clinical data of 830 consecutive patients who presented with uveitis at a tertiary referral center in northern Taiwan between August 2013 and August 2020 were analyzed. The clinical characteristics and outcomes of patients with NNUMS were evaluated. RESULTS: Overall, 3.7% of patients were determined to have uveitis masquerade syndrome. Among them, 24 patients (77%; 34 eyes) were diagnosed as having NNUMS. The main presenting anatomical location was posterior uveitis (58.8%). In the NNUMS group, a high chorioretinal involvement rate (94.1%) and delayed diagnosis from symptom onset (45.8% cases were diagnosed after more than 90 days) were found. Multimodal imaging was the major decisive diagnostic factor. Systemic condition alterations requiring urgent treatment were noted in 29.2% of cases. Ocular complications were noted in 58.8% of cases; 60% of those were observed on referral. Following appropriate treatment, visual acuity could be maintained in 88.3% of cases. The 5 major categories of NNUMS were retinal vascular disorders, rhegmatogenous retinal detachment, retinal dystrophy, central serous chorioretinopathy, and uveal effusion syndrome. CONCLUSION: NNUMS is a group of heterogeneous diseases with a complex diagnostic process and significant ocular and systemic effects. High awareness regarding common clinical manifestations is crucial for physicians to make the appropriate diagnosis and management.

Clinical and Epidemiological Profiles of Retinal Vasculitis in Northern Taiwan.

PURPOSE: To investigate the epidemiological and clinical profiles in retinal vasculitis in an Asian cohort. METHODS: A 5-year retrospective study of 487 uveitis patients in a tertiary referral center at northern Taiwan. RESULTS: Overall, 18.5% of the cases were associated with retinal vasculitis (RV). Sarcoidosis and cytomegalovirus retinitis were two leading diagnoses. Cases with RV were younger (mean: 39.7 years), less unilateral (50%), and had more chorioretinal involvement (95.5%). Definite diagnosis was reached in 86.7% of RV cases, of which 38.5% had infectious uveitis. While sole arteritis was presented in 8.9% of cases, 63.3% showed phlebitis, and 27.8% involved both. Three distinctive patterns were associated with a higher likelihood of infection: nodular sheathing, continuous perivascular sheathing (OR 4.79), and continuous fluorescein leakage (OR 4.11). CONCLUSION: The presence of RV, especially arteritis, is highly suggestive of identifiable etiology. Distinctive clinical patterns help differentiation of infectious versus noninfectious causes.

Ocular inflammatory manifestations following COVID-19 vaccinations in Taiwan: A case series.

As a continuing demand for booster shots against SARS-CoV-2, ocular adverse events following the coronavirus disease-2019 (COVID-19) vaccines can cause significant visual impairment, and they warrant a high awareness and detailed documentation of possible ocular inflammatory manifestations. We present a case series of 11 patients presenting with ocular manifestations relevant to vaccine-associated autoimmune response within 6 weeks after the vaccination of the Oxford-AstraZeneca, the Moderna, and Pfizer-BioNTech vaccines at the main tertiary referral center in the most populated and most vaccinated city in Taiwan. Their diagnosis included five acute anterior uveitis, two multiple evanescent white dot syndrome, one probable Vogt-Koyanagi-Harada disease, one anterior scleritis, one relapsed idiopathic panuveitis, and one autoantibody-related central retinal artery occlusion. This report presented a broad spectrum of the ocular inflammatory events following the vaccination of COVID-19. Early recognition of the clinical manifestations mentioned herein with prompt management is crucial in recovering the patients' vision.

Combined intravitreal ranibizumab and posterior subtenon triamcinolone acetonide injections for patients with diabetic macular edema refractory to intravitreal ranibizumab monotherapy.

PURPOSE: The purpose of this study is to compare the efficacy of intravitreal ranibizumab (IVR) alone and concurrent IVR with posterior subtenon triamcinolone acetonide (PSTA) injection for patients with diabetic macular edema (DME) refractory to IVR monotherapy. MATERIALS AND METHODS: We enrolled 43 eyes of 43 patients with DME who received at least three times of IVR, which resulted in poor anatomical responses, with central foveal thickness (CFT) reduction <10% and postinjection CFT >300 µm. All the eyes received initial 3 monthly then pro re nata (PRN) IVR 0.5-mg injections. Twenty eyes continued PRN injections and 23 eyes received combined IVR 0.5 mg and PSTA 40 mg with at least 1-year follow-up. Best-corrected visual acuity (BCVA) and CFT were recorded from 1-month to 1-year follow-up. RESULTS: Following switch to combined therapy, the mean BCVA significantly improved from 0.61 ± 0.32 logarithm of the minimum angle of resolution (logMAR) to 0.45±0.39 logMAR at 6 month (P = 0.003), 0.43±0.35 logMAR at 9 months (P < 0.001), and 0.48±0.45 logMAR at 1 year (P = 0.03). In eyes with IVR alone, no significant VA improvement was noted throughout the year. Significantly better BCVA was noted in the combined group at 6-month, 9-month, and 1-year follow-up compared to IVR-alone group. The timing of combined therapy showed a significant association with 1-year BCVA (t = 3.25, P = 0.018). CONCLUSION: Concurrent IVR and PSTA resulted in significantly better visual outcomes in 1-year follow-up for those refractory to preceding ranibizumab monotherapy for DME. Early addition of PSTA predicted a better visual outcome.

Comparison of Intravitreal Dexamethasone Implant and Ranibizumab in Vitrectomized Eyes with Diabetic Macular Edema.

PURPOSE: This retrospective study aimed to compare the efficacy of intravitreal ranibizumab (IVR) and intravitreal dexamethasone implant (IDI) for pseudophakic vitrectomized eyes with diabetic macular edema (DME) in a single institution. METHODS: Pseudophakic vitrectomized eyes with treatment-naïve center-involved DME were enrolled, with one eye in each patient. They were divided into two groups: one group receiving IDI every 3 to 4 months and another group receiving IVR using 3 monthly plus treat-and-extend injections, all with monthly follow-up for 6 months. Switch of intravitreal drugs or deferred macular laser was not allowed. Primary outcome measures included change in central foveal thickness (CFT) in 1 mm by spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) at Month 6. RESULTS: Twenty-two eyes were included in the IDI group and 26 eyes in the IVR group. The baseline demographics, glycosylated hemoglobin level, intraocular pressure (IOP), BCVA, and CFT did not significantly differ (p > 0.05). Compared to baseline data, CFT decreased and BCVA improved significantly after either IDI or IVR at Month 6 (p < 0.05). Significantly better mean final BCVA (0.38 logMAR vs. 0.62 logMAR, p=0.04), more mean visual gain (-0.30 logMAR vs. -0.15 logMAR, p=0.02), lower mean final CFT (310.9 µm vs. 384.2 µm, p=0.04), and larger mean CFT decrease (-150.0 µm vs. -60.1 µm, p=0.03) were found in the IDI group compared to those in the IVR group. A smaller mean treatment number (2.6 vs. 5.6, p < 0.001) and higher rate of postinjection ocular hypertension requiring topical hypotensive agent therapy (27.3% vs. 0%, p=0.0002) were demonstrated in the IDI group than those in the IVR group. CONCLUSION: We concluded that IDI and IVR can both effectively treat vitrectomized eyes with DME. Dexamethasone implants had significantly better visual/anatomical improvement, smaller treatment number, and higher rate of elevated IOP after injection than IVR in pseudophakic vitrectomized eyes with DME in a 6-month period.

Effect of medications after cardiac surgery on long-term outcomes in patients with cirrhosis.

ABSTRACT: The aim of this study was to evaluate the effect of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) after cardiac surgery in the liver cirrhosis (LC) patients. We conducted a population-based cohort study using data from the Taiwanese National Health Insurance Research Database (NHIRD) from 2001 to 2013. The outcomes of interest included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE) and liver and renal outcomes. Among 1470 LC patients, 35.6% (n = 524) received beta-blockers and 33.4% (n = 491) were prescribed ACEIs and/or ARBs after cardiac surgery. The risk of negative liver outcomes was significantly lower in the ARB group compared with the ACEI group (9.6% vs 22.7%, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.31-0.83). Furthermore, the risk of MACCE (44.2% vs 54.7%, HR 0.79, 95% CI 0.65-0.96), all-cause mortality (35.3% vs 46.4%, HR 0.74, 95% CI 0.60-0.92), composite liver outcomes (9.6% vs 16.5%, HR 0.56, 95% CI 0.38-0.85) and hepatic encephalopathy (2.7% vs 5.7%, HR 0.45, 95% CI 0.21-0.94) were lower in the ARB group than the control group. Our study demonstrated that ARBs provide a greater protective effect than ACEIs in regard to long-term outcomes following cardiac surgery in patients with LC.

Impact of massive blood transfusion during adult extracorporeal membrane oxygenation support on long-term outcomes: a nationwide cohort study in Taiwan.

OBJECTIVES: Bleeding is a common problem during adult extracorporeal membranes oxygenation (ECMO) support, requiring blood transfusion for correction of volume depletion and coagulopathy. The goal of this study is to investigate the long-term outcomes for adults under support of ECMO with massive blood transfusion (MBT). DESIGN: Retrospective nationwide cohort study. SETTING: Data were provided from Taiwan National Health Insurance Research Database (NHIRD). PARTICIPANTS AND INTERVENTIONS: Totally 2757 adult patients were identified to receive MBT (red blood cell ≥10 units) during ECMO support from 2000 to 2013 via Taiwan NHIRD. MAIN OUTCOME MEASURES: The outcomes included in-hospital major complications/mortality, all-cause mortality, cardiovascular death, newly onset end-stage renal disease and respiratory failure during the follow-up period. RESULTS: Patients with MBT had higher in-hospital mortality (65.6% vs 52.1%; OR 1.74; 95% CI 1.53 to 1.98) and all-cause mortality during the follow-up (47.0% vs 35.8%; HR 1.46; 95% CI 1.25 to 1.71) than those without MBT. Not only higher incidences of post ECMO sepsis, respiratory failure and acute kidney injury, but also longer duration of ECMO support, ventilator use and intensive care unit stay were demonstrated in the MBT group. Moreover, a subdistribution hazard model presented higher cumulative of respiratory failure (19.8% vs 16.2%; subdistribution HR 1.36; 95% CI 1.07 to 1.73) for the MBT cohort. Positive dose-dependent relationship was found between the amount of transfused red blood cell product and in-hospital mortality. In the MBT subgroup analysis for the impact of transfused ratio (fresh frozen plasma/packed red blood cell) on in-hospital mortality, ratio ≥1.0 had higher mortality. CONCLUSIONS: Patients with MBT during ECMO support had worse long-term outcomes than non-MBT population. The transfused amount of red blood cell had positive dose-dependent effect on in-hospital mortality.

Effect of massive blood transfusion on late outcomes after surgical repair of acute type A aortic dissection.

Massive blood transfusion (MBT) increased mortality and morbidity after cardiac surgery. However, a mid-term follow-up study on repair surgery of acute type A aortic dissection (AAAD) with MBT was lacking. This study aimed to assess the impact of perioperative MBT on late outcomes of surgical repair for AAAD.There were 3209 adult patients firstly received repair surgery for AAAD between 2005 and 2013, were identified using Taiwan National Health Insurance Research Database. Primary interest variable was MBT, defined as transfused red blood cell (RBC) ≥10 units.The outcomes contained in-hospital mortality, surgical-related complications, all-cause mortality, respiratory failure, and chronic kidney disease (CKD) during follow-up period. Higher in-hospital mortality (37.7% vs 11.6%; odds ratio, 4.00; 95% confidence interval [CI], 3.30-4.85), all-cause mortality (26.1% vs 13.0%; hazard ratio [HR], 1.66; 95% CI, 1.36-2.04), and perioperative complications were noted in the MBT group. A subdistribution hazard model revealed higher cumulative incidence of CKD (13.9% vs 6.5%; HR, 1.95; 95% CI, 1.47-2.60) and respiratory failure (7.1% vs 2.7%; HR, 2.34; 95% CI, 1.52-3.61) for the MBT cohort. A dose-dependent relationship between amount of transfused RBC (classified as tertiles) and cumulative incidence of all-cause mortality, incident CKD, and respiratory failure was found (P of trend test <.001).Patients with MBT had worse late outcomes following surgical repair of AAAD. The cumulative incidence of all-cause mortality, incident CKD, and respiratory failure increased with the amount of transfused RBC in a dose-dependent manner.

Intravitreal aflibercept versus bevacizumab for treatment of myopic choroidal neovascularization.

The authors performed a retrospective and comparative study to compare the efficacy of intravitreal aflibercept and bevacizumab for patients with myopic choroidal neovascularization (mCNV). The patients with treatment-naïve mCNV received 1 + PRN intravitreal bevacizumab from March 2008 to February 2013, while from March 2013 to July 2016 patients were treated by 1 + PRN intravitreal aflibercept, all with monthly follow-up for 12 months. Primary outcome measures included change in central foveal thickness (CFT) in 1 mm by spectral-domain optic coherence tomography, and best corrected visual acuity (BCVA) at month 12. Complications after injections were recorded. The intra-group changes in CFT and BCVA were compared with Wilcoxon signed rank test, the between-group difference compared with Wilcoxon rank sum test. Fisher's exact test was used for categorical comparison between groups. Seventy-eight eyes of 78 patients were collected. There were 42 eyes in bevacizumab group, with mean age of 53.2 ± 5.4 years and 27 female patients of them. The mean BCVA significantly improved from baseline 0.56 ± 0.35 logMAR to 0.35 ± 0.35 logMAR at Month 12 after bevacizumab treatment (p < 0.001). The mean CFT significantly decreased from baseline 315.3 ± 25.6 µm to 253.7 ± 24.4 µm at Month 12 following intravitreal bevacizumab (p < 0.001). There were 36 eyes in aflibercept group, with mean age of 52.8 ± 6.8 years and 24 female patients of them. The mean BCVA significantly improved from baseline 0.61 ± 0.47 logMAR to 0.38 ± 0.41 logMAR at Month 12 after aflibercept treatment (p < 0.001). The mean CFT significantly decreased from baseline 328.2 ± 19.8 µm to 241.8 ± 27.2 µm at Month 12 following intravitreal aflibercept (p < 0.001). The baseline demographics, lens status, axial length, refractive errors, duration of symptoms, BCVA, and CFT did not differ significantly between groups (p > 0.05). There was no significant difference between bevacizumab and aflibercept groups in BCVA and CFT from Month 1 to Month 12 (p > 0.05). Injection number of aflibercept was 2.11 ± 0.41, less than that of bevacizumab (3.23 ± 0.38) during 12-month period (p = 0.01). There were no systemic thromboembolic event, elevated intraocular pressure, retinal detachment, or infectious endophthalmitis following injections in both groups. We concluded that both aflibercept and bevacizumab can effectively treat choroidal neovascularization in high myopes. Intravitreal aflibercept had similar efficacy but less treatment number than bevacizumab for mCNV during 12-month period.

Postoperative Renal Outcomes of Patients Receiving Percutaneous Nephrolithotomy versus Pyelolithotomy: A Population-Based Cohort Study.

The aim of this population-based cohort study was to explore postoperative renal outcomes of patients receiving pyelolithotomy versus percutaneous nephrolithotomy (PCNL). Data were retrieved from the Taiwan National Health Insurance Research Database. During the period from Jan 1, 1998, to Dec 31, 2012, there were 2549 and 21654 patients who underwent pyelolithotomy and PCNL, respectively. The postoperative incidence of new diagnosed end stage renal disease (ESRD) was statistically analyzed and compared between the pyelolithotomy and PCNL groups. The perioperative complications of two groups were also analyzed. In comparison to pyelolithotomy, PCNL achieved lower new diagnosed ESRD (1.38% versus 2.28%, p = 0.0004). Patients receiving PCNL had significantly higher rates of preoperative hypertension, diabetes mellitus, pulmonary disease, cerebrovascular disease, and coronary artery disease. The hospital stay was shorter in PCNL groups compared with pyelolithotomy groups (8.31 days versus 12.59 days, p = 0.0006). In conclusion, PCNL contributed to lower rates of new diagnosed ESRD and hospital stay when compared to pyelolithotomy.

Comparison of efficacy of intravitreal ranibizumab between non-vitrectomized and vitrectomized eyes with diabetic macular edema.

PURPOSE: To compare the efficacy of intravitreal ranibizumab between non-vitrectomized and vitrectomized eyes with diabetic macular edema (DME). STUDY DESIGN: A retrospective, nonrandomized, and comparative study. METHODS: From May 2013 to March 2016, 148 eyes of 148 patients with treatment-naïve center-involving DME were reviewed in one institution. Forty-six eyes underwent prior vitrectomy at least 3 months ago, and 102 eyes did not receive any vitrectomy. Three monthly then PRN intravitreal ranibizumab treatments were performed in all the patients with monthly follow-up for 6 months. Primary outcome measures included change in central foveal thickness (CFT) and best-corrected visual acuity (BCVA) at month 6. RESULTS: The CFT significantly reduced, and the BCVA significantly improved 6 months after ranibizumab injections in either vitrectomized or non-vitrectomized groups (p < 0.05). There was no difference between vitrectomized and non-vitrectomized eyes in baseline characteristics. Significantly better final BCVA and visual gain were found in non-vitrectomized eyes than in vitrectomized eyes (p = 0.01 and 0.03, respectively). Final CFT and CFT decrease were significantly greater in non-vitrectomized group than in vitrectomized group (p = 0.02 and 0.006, respectively). Injection number of ranibizumab was 4.12 ± 0.58 in non-vitrectomized eyes, significantly less than that in vitrectomized eyes (5.05 ± 0.71) during 6-month period (p < 0.001). There were no severe systemic/ocular adverse effects in both groups. CONCLUSIONS: Intravitreal ranibizumab was helpful for either vitrectomized or non-vitrectomized eyes with DME in short-term follow-up. Anatomical and functional improvements were greater in non-vitrectomized patients than in vitrectomized cases.

Laser and Anti-Vascular Endothelial Growth Factor Agent Treatments for Retinal Arterial Macroaneurysm.

PURPOSE: To describe the efficacy of laser and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents for patients with symptomatic retinal arterial macroaneurysm (RAM). DESIGN: From 2009 to 2016, we collected patients with exudative or hemorrhagic RAM all treated by focal laser photocoagulation. METHODS: Nd:YAG laser was performed in patients with subinternal limiting membrane (sub-ILM) hemorrhage. Intravitreal anti-VEGF agents were given in eyes with macular exudation as adjuncts. Changes of visual acuity and central foveal thickness before and after treatment were recorded and compared with Wilcoxon signed-rank test. RESULTS: Thirty-five eyes that underwent a single session of laser photocoagulation for RAM resulted in macroaneurysm regression. The hemorrhagic group included 24 eyes having ruptured macroaneurysms without macular exudation. Five eyes with simultaneous sub-ILM hemorrhage receiving Nd:YAG laser membranotomy had resolution of preretinal hemorrhage. Exudative RAM having cystoid macular edema or submacular fluid with or without ruptured macroaneurysms was treated by focal laser photocoagulation alone in 3, or combined with single intravitreal anti-VEGF agent in 8 eyes. All patients had significantly improved vision when comparing visual acuity at baseline and final follow-up (P = 0.00016). Significant reduction of macular thickness was also observed after laser monotherapy or combined treatment in exudative RAM (P = 0.018). CONCLUSIONS: Focal laser photocoagulation was helpful for the management of ruptured or leaky RAM. Combined focal laser and intravitreal anti-VEGF agents could better reduce macular exudation caused by RAM. Additionally, Nd:YAG laser was a safe and effective method to remove the sub-ILM hemorrhage caused by RAM.

Comparison of the Efficacy of Intravitreal Aflibercept and Bevacizumab for Macular Edema Secondary to Branch Retinal Vein Occlusion.

Fifty-two eyes of 52 patients with treatment-naïve macular edema associated with perfused branch retinal vein occlusion were retrospectively reviewed. Twenty-seven cases received PRN intravitreal bevacizumab, and 25 cases were treated by PRN intravitreal aflibercept with monthly follow-ups for 12 months. Both aflibercept and bevacizumab were effective in reduction of macular thickness and improvement of visual acuity for the participants. Both antivascular endothelial growth factor agents had similar efficacy and duration of treatment for these eyes with macular edema secondary to branch retinal vein occlusion during a 12-month period. No serious systemic or ocular adverse events were reported.

The protective effects of the proteasome inhibitor bortezomib (velcade) on ischemia-reperfusion injury in the rat retina.

PURPOSE: To evaluate the protective effects of bortezomib (Velcade) on ischemia-reperfusion (IR) injury in the rat retina. METHODS: The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg), or high-dose bortezomib (0.2 mg/kg) before the induction of IR injury. Electroretinography (ERG) was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α), anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin), and pro-apoptotic proteins (p53, bax) were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein), NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells. RESULTS: ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group. CONCLUSIONS: Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

Anti-inflammatory effect of the proteasome inhibitor bortezomib on endotoxin-induced uveitis in rats.

PURPOSE: We evaluated the anti-inflammatory effect of bortezomib (Velcade), a proteasome inhibitor, on endotoxin-induced uveitis (EIU) in rats and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. METHODS: EIU was induced by footpad injection of LPS into Lewis rats. MG-132 (10 mg/kg), or high-dose (0.2 mg/kg) or low-dose (0.05 mg/kg) bortezomib was given 30 minutes before LPS injection in each treatment group. The rats were sacrificed 24 hours later to observe the inflammatory response in tissues. The expression levels of fractalkine, MCP-1, ICAM-1, and iNOS were evaluated by PCR and Western blot analysis. Immunohistochemical (IHC) studies were used to demonstrate the expression of pro-inflammatory mediators and nuclear factor-kappa B (NF-κB) p65 in the iris and ciliary body. The DNA-binding activity of NF-κB was evaluated using an electrophoretic mobility shift assay (EMSA). An in vitro study using RAW 264.7 cells was performed to verify the results. RESULTS: Pretreatment with high-dose bortezomib significantly attenuated the inflammatory response of EIU. Reduced expression of inflammatory mediators always was observed in the high-dose bortezomib and MG-132 groups, but invariably was not noted in the low-dose bortezomib group. Decreased DNA-binding activity of NF-κB was noted in those rats pretreated with high-dose bortezomib or MG-132. In vitro study demonstrated the dose-dependent anti-inflammatory effects of bortezomib in LPS-stimulated RAW cells, consistent with the results obtained in vivo. CONCLUSIONS: Bortezomib inhibits EIU, probably by inhibiting the activation of NF-κB, which in turn, down-regulates the expression of the associated inflammatory genes. Proteasome inhibition may be a potential treatment strategy for uveitis.

Intravitreal gas injection for macular hole with localized retinal detachment in highly myopic patients.

PURPOSE: This study aimed to evaluate treatment effects of intravitreal gas for macular hole with localized retinal detachment (RD) in highly myopic eyes and to examine how the vitreomacular relationship and other factors may influence treatment outcomes. METHODS: Twenty highly myopic patients with macular holes and localized posterior RD, treated initially with intravitreal injection of C(3) F(8) , were prospectively studied. Recurrent disease was treated with repeated gas injection or vitrectomy according to the extent of detachment. Length of follow-up was ≥ 12 months. Vitreomacular conditions were determined before and within 2 months after gas injection by standard optical coherence tomography. Demographics, refractive errors, axial length, the extent of chorioretinal (CR) atrophy and visual acuity were recorded. RESULTS: The success rate after primary gas injection was 70%. The remaining 30% of patients achieved anatomic success after further treatment, including vitrectomy with gas or silicone oil tamponade and/or scleral buckling. All cases achieved anatomic success after a mean of 1.4 surgeries. Univariate analysis showed that the patterns of the posterior vitreoretinal relationship did not differ significantly between those successfully treated with gas only (group 1) and those requiring vitrectomy (group 2) (p = 1.000). Logistic regression showed no statistically significant differences in any characteristics between groups 1 and 2. CONCLUSIONS: Intravitreal gas tamponade alone may achieve anatomic success in more than two-thirds of highly myopic patients with macular holes and localized RD. Patients with different clinical characteristics and vitreoretinal relationships seem to have similar opportunities to achieve reattachment through this relatively non-invasive surgery.