Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Predictive factors for functional improvement after intravitreal bevacizumab therapy for macular edema due to branch retinal vein occlusion

To identify predictive factors for improvement of visual acuity and central retinal thickness by intravitreal bevacizumab for the treatment of macular edema (ME) due to branch retinal vein occlusion (BRVO). Two hundred and five eyes from 204 patients with ME secondary to BRVO were retrospectively included at six sites. All eyes received intravitreal bevacizumab therapy (1.25 mg/0.05 ml). The mean follow-up was 36.8 +/- 12.7 weeks (range, 18 to 54 weeks). Measurement of ETDRS best-corrected visual acuity (BCVA, in all eyes) and optical coherence tomography (OCT, in 87% of eyes) were performed at baseline and at follow-up examinations every 12 weeks. Using fluorescein angiography, the perfusion status of the macula at baseline could be assessed in 84% of the eyes. The main outcome measures were changes in BCVA and central retinal thickness (CRT). For analysis of predictive factors, the results at 24 weeks were used. The median BCVA was 0.6 LogMAR at baseline and improved to 0.4 LogMAR at 24 and 48 weeks. This visual improvement was associated by a significant reduction in CRT, decreasing from a baseline of 454 mu m to 267 mu m and 248 mu m after 24 and 48 weeks respectively. Eyes with ME and intact (perfused) or interrupted (ischemic) foveal capillary ring showed a 2-line increase of median BCVA [45 eyes (22%) and 128 eyes (62%) respectively]. However, the final median BCVA was significantly worse in eyes with ischemic ME (0.6 versus 0.3 logMAR in perfused ME). Other factors for visual improvement were absence of previous treatments of the ME, age younger than 60 years and low baseline BCVA (a parts per thousand yen0.6 logMAR) (2, 3, and 2 median BCVA lines increase respectively). Furthermore, eyes with duration of the ME of less than 12 months responded with a 3-line increase of the median BCVA. Final CRT only showed minor differences between the subgroups. During the entire follow-up, retreatments were performed in 85% of the eyes, with a median number of injections of three (mean 3.2; range, 1 to 10) and a median time-interval between injections of 11.6 weeks (mean 14.6 weeks). Intravitreal injection of bevacizumab resulted in a significant improvement of BCVA and reduction of ME in BRVO. Baseline BCVA, patient's age, and duration of BRVO were found to be of prognostic relevance for visual improvement. A less favorable outcome of the bevacizumab therapy in eyes with longstanding BRVO would advocate initiation of treatment within 12 months after onset

Evaluation of 3D heads-up vitrectomy: outcomes of psychometric skills testing and surgeon satisfaction

OBJECTIVES: To evaluate the use of a three-dimensional heads-up microscope (3DM) during 25-gauge pars plana vitrectomy (PPV) compared with a traditional ophthalmic microscope (TM) in terms of efficacy, safety, and teaching and learning satisfaction. METHODS: Prospective comparative interventional study. Fifty eyes affected by one of the following diseases: rhegmatogenous or tractional retinal detachment, epiretinal membrane, full-thickness macular hole, vitreous hemorrhage, or dropped lens. The 50 eyes were randomly assigned to one of two groups: group A (25 eyes) underwent 25-gauge PPV with 3DM, and group B (25 eyes) underwent 25-gauge PPV with TM. The main outcome measures were the duration of the operation, intraoperative complications, and surgeon and observer satisfaction. A questionnaire was used to assess surgeon satisfaction according to the following parameters: comfort, visibility, image quality, depth perception, simplicity of use, maneuverability, and teaching. A questionnaire to assess observer satisfaction was completed by 20 observers (surgical residents or ophthalmic surgeons). RESULTS: The degree of satisfaction was higher using 3DM for both surgeons and observers (P < 0.001). The average duration of the operation did not differ significantly between the two methods. No major complications occurred for either method. CONCLUSIONS: PPV with 3DM is more comfortable for the surgeon and poses no substantially greater risk of complications for the patient. The high-definition screen delivers excellent depth perception and better screen parameter control, which results in high-quality surgical performance. 3DM surgery helps to significantly improve teaching and learning intra-operative surgical procedure