Anterior chamber aqueous flare is not a predictor for surgical closure of full-thickness idiopathic macular holes.

PURPOSE: To investigate the predictive value of preoperative anterior chamber aqueous flare levels measured by laser flare photometry for surgical success of idiopathic macular holes in addition to preoperative anatomic characteristics. METHODS: Records of 105 consecutive eyes with full-thickness idiopathic macular holes which underwent pars plana vitrectomy with internal limiting membrane peeling and sulfur hexafluoride 20% (SF620%) endotamponade were reviewed retrospectively. All patients underwent preoperative measurements of anterior chamber aqueous flare and anatomical idiopathic macular hole characteristics evaluated by optical coherence tomography: macular hole inner opening diameter, macular hole minimum linear diameter, macular hole base diameter, and macular hole height. Best-corrected visual acuity results were recorded pre- and postoperatively. RESULTS: In 17 (16.2%) of 105 eyes primary closure of idiopathic macular hole failed, whereas in 88 eyes (83.8%) closure was achieved. Between both groups, preoperative macular hole minimum linear diameter (p = 0.001) and macular hole inner opening diameter (p = 0.006) were statistically different. Failure rates were significantly lower in eyes with macular hole minimum linear diameter < 400 µm (7.4% vs 32.4%; p = 0.013) and preoperative macular hole minimum linear diameter showed moderate correlation with pre- and postoperative best-corrected visual acuity results (r = 0.512; p < 0.001; r = 0.612; p < 0.001). Mean anterior chamber aqueous flare of 11.5 ± 9.9 pc/ms in eyes with anatomical closure and 11.8 ± 6.4 pc/ms in unclosed cases was comparable (p = 0.28) and did not correlate with anatomical or functional results. CONCLUSION: Eyes with idiopathic macular hole ⩾ 400 µm in size have a significantly higher failure rate following standardized pars plana vitrectomy with internal limiting membrane peeling and SF620% endotamponade. Preoperative macular hole minimum linear diameter and macular hole inner opening diameter seem to be associated with surgical outcome in idiopathic macular hole, whereas anterior chamber aqueous flare level does not provide additional predictive value.

A Randomized Controlled Clinical Trial Comparing 20 Gauge and 23 Gauge Vitrectomy for Patients with Macular Hole or Macular Pucker.

INTRODUCTION: To compare the transconjunctival sutureless 23 gauge (G) pars plana vitrectomy (PPV) with 20 G PPV regarding inflammation, safety, visual outcome and patient comfort. METHODS: We included 103 patients with symptomatic macular hole or macular pucker, scheduled for vitrectomy in this prospective, randomized, controlled, mono-center clinical trial. Patients were randomized 1:1 to either 20G PPV (n = 51) or 23G PPV (n = 52). All eyes underwent standard 20G or 23G PPV with membrane peeling. Primary outcome measure was change in aqueous humor flare 3 weeks after surgery compared with baseline. Secondary outcome measures were flare values 2 days and 26 weeks after surgery, subjective discomforts measured with a visual analog scale, best-corrected visual acuity, duration of surgery, intraocular pressure (IOP) and adverse events. RESULTS: There was no significant difference in change of flare 3 weeks after PPV [- 1.7, 95% CI (- 6.3 to 2.9), p = 0.466]. Both groups showed a significant increase in flare 2 days after surgery (20G: p < 0.001, 23G: p = 0.002), but only the 20G group after 3 weeks (p = 0.011). The gain in visual acuity after 3 weeks was higher after 23G PPV (4.2 95% CI (0.4-8.0, p = 0.029), but without a difference after 6 months. The duration of surgery was shorter in the 23G group (p < 0.001). Patient comfort 3 weeks after surgery was greater after 23G PPV (foreign body sensation p = 0.002; itching: p = 0.021). However, the rate of complications did not differ between the groups. CONCLUSION: The primary aim, showing the superiority of the 23G group regarding the change of flare value from baseline to 3 weeks after surgery, was not met, but the level of inflammation decreased faster after 23G PPV. Clear advantages of the 23G PPV were a lower risk of postoperative IOP elevation, a shorter surgery time, faster visual recovery and greater patient comfort in the early postoperative phase. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01969929.

Multiplex Cytokine Analysis of Aqueous Humor in Juvenile Idiopathic Arthritis-Associated Anterior Uveitis With or Without Secondary Glaucoma.

Patients with juvenile idiopathic arthritis often develop chronic anterior uveitis (JIAU). JIAU patients possess a particularly high risk for developing secondary glaucoma when inflammatory inactivity has been achieved. By using multiplex bead assay analysis, we assessed levels of pro- and anti-inflammatory cytokines, chemokines, or metalloproteinases in the aqueous humor (AH) of patients with clinically inactive JIAU with (JIAUwG) or without secondary glaucoma (JIAUwoG), or from patients with senile cataract as controls. Laser-flare photometry analysis prior to surgery showed no significant differences between JIAUwG or JIAUwoG. Compared with the control group, levels of interleukin-8, matrix metalloproteinase-2, -3, -9, serum amyloid A (SAA), transforming growth factor beta-1, -2, -3 (TGFß-1, -2, -3), and tumor necrosis factor-alpha in the AH were significantly higher in patients with clinically inactive JIAUwG or JIAUwoG. Samples from JIAwoG patients displayed significantly higher levels of SAA (P < 0.0116) than JIAUwG patients. JIAUwG patients showed an increased level of TGFß-2 in AH samples compared with JIAUwoG (P < 0.0009). These molecules may contribute to the clinical development of glaucoma in patients with JIAU.

Conditions of retinal glial and inflammatory cell activation after irradiation in a GFP-chimeric mouse model.

PURPOSE: Microglia cells have been associated with immunologic defense and repair. The course of retinal disease after lethal irradiation for bone marrow depletion and substitution was evaluated with respect to macrophage and microglial involvement. METHODS: Lethal irradiation in C57BL/6 mice was conducted with a low-voltage radiation unit. The animals were randomized to shielded or unshielded radiation and subsequently received transplants of GFP+ bone marrow cells (beta-actin promoter). The GFP transformation rate was analyzed by flow cytometry. GFP+ cells in the retina were examined for co-localization with macrophage and dendritic cell markers at various time points between 1 and 7 months after irradiation. Clodronate liposomes were used to investigate the fate of migrated and residential microglia cells. Pathologic angiogenesis was investigated in laser-induced choroidal neovascularization (CNV) after unshielded and shielded irradiation. RESULTS: Flow cytometry revealed average transformation rates of 78.2% in unshielded and 64.1% in shielded group. Four weeks after transplantation, perfused flat mounts were virtually free of extravasal GFP+ cells in both groups, whereas 4 months after irradiation, cluster cell infiltrations, preferentially in the peripheral retina, became apparent exclusively in the unshielded group. Cell morphology ranged from oval, to a few extensions, to dendritiform with long-branched extensions. Clodronate treatment resulted in a reduction of GFP+ cells in the retinal tissue when applied 3 months after unshielded irradiation. Although GFP+ cells accumulated in the choroidal scar after laser treatment, in both the shielded and unshielded groups, GFP+ cells in the overlying retina were restricted to the unshielded group. CONCLUSIONS: Approximately 3 months after lethal full-body irradiation including the eye, bone marrow-derived leukocytes exhibit a wound-healing reaction, and unlike physiological turnover, infiltrate the retina and form microglial cells.

Inhibition of TNF-alpha reduces laser-induced choroidal neovascularization.

To investigate the role of the TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in a mouse model. Four separate laser burns were applied to induce ruptures of Bruch's membrane and subsequent choroidal neovascularization in C57BL/6J mice. TNF-alpha protein expression was semiquantitatively assessed by Western blot analysis of the choroidal and RPE layer from mice with or without laser treatment. To investigate the effect of TNF-alpha inhibition on CNV formation, animals were treated for 7 days via intraperitonealy implanted osmotic pumps either 3 days before or after laser injury with recombinant TNF receptor P75 (etanercept), a chimeric monoclonal antibody (infliximab), or a purified rat anti-mouse/rat TNF monoclonal antibody (TNF-mAb), respectively. Fluorescein angiography, flat-mount preparations, and histopathology were performed at day 7, 10, or 14 after laser treatment. Western blotting demonstrated that TNF-alpha expression was 4.57-fold higher in the choroid and RPE one week after laser injury compared to control mice without laser. When evaluated one and two weeks after laser injury, etanercept and infliximab given from the 3rd day before laser-damage significantly reduced CNV size and pathological fluorescein leakage compared to the control group after laser treatment only. The inhibitory effect of the monoclonal TNF-alpha antibody on CNV formation was evident two weeks after photocoagulation but not after one week. Only etanercept administered 3 days after laser injury still reduced significantly the development of CNV lesions. Histopathology confirmed that CNV lesions in treated mice were smaller in size compared to the control animals without TNF inhibitor treatment. In conclusion, anti-TNF-alpha treatment with different inhibitors reduces both the size and the leakage of laser-induced CNV. These results suggest the involvement of TNF-alpha in the development of laser-induced CNV and its potential use as a therapeutic agent in the age-related macular degeneration.