Large upper eyelid full-thickness defects reconstructed only with an anterior lamella.

BACKGROUND: The purpose of this study is to report a surgical procedure that only uses anterior lamella structures (muscle and skin) to reconstruct large upper eyelid full-thickness total defects. PATIENTS AND METHODS: The study design is a non-comparative retrospective interventional small case series. Three patients with upper eyelid full-thickness (anterior and posterior lamellae) total-defect (horizontal extent: > 3/4 length, vertical extent: > 15 mm) after tumor excision (basal cell, squamous cell, or Merkel's cell carcinoma). As intervention an eyelid reconstruction using only a rotation/advancement muscular-skin flap was used. The outcome was postoperatively an upper eyelid anatomic cosmetic-appearance and lid-closure function. RESULTS: Good anatomic cosmetic-appearance and lid-closure function were achieved soon after surgery. No remarkable ocular as well as extra-ocular side effects or complications were noted. CONCLUSIONS: In a single-stage procedure it appears possible to repair upper eyelid full-thickness total defects by reconstructing only the anterior lamella. With this procedure there is no need to reconstruct the posterior lamella and/or to use tissue from other eyelids or parts of the body.

Lentiviral-vector-mediated expression of murine IL-1 receptor antagonist or IL-10 reduces the severity of endotoxin-induced uveitis.

Uveitis is a sight threatening inflammatory disorder that remains a significant cause of visual loss. We investigated lentiviral gene delivery of interleukin 1 receptor antagonist (IL-1ra) or interleukin (IL)-10 to ameliorate murine endotoxin-induced uveitis (EIU). An human immunodeficiency virus-1-based vector containing the mIL-1ra or mIL-10 cDNA demonstrated high expression of biologically active cytokine. Following administration of Lenti.GFP into the anterior chamber, transgene expression was observed in corneal endothelial cells, trabecular meshwork and iris cells. To treat EIU, mice were injected with Lenti.IL-1ra, Lenti.IL-10 or a combination of these. EIU was induced 14 days after vector administration and mice were culled 12 h following disease induction. Lenti.IL-1ra or Lenti.IL-10-treated eyes showed significantly lower mean inflammatory cell counts in the anterior and posterior chambers compared with controls. The aqueous total protein content was also significantly lower in treated eyes, demonstrating better preservation of the blood-ocular barrier. Furthermore, the treated eyes showed less in vivo fluorescein leakage from inner retinal vessels compared with controls. The combination of both IL-1ra and IL-10 had no additive effect. Thus, lentiviral gene delivery of IL-1ra or IL-10 significantly reduces the severity of experimental uveitis, suggesting that lentiviral-mediated expression of immunomodulatory genes in the anterior chamber offers an opportunity to treat uveitis.

[Lower eyelid reconstruction of traumatically caused cicatricial entropion with amniotic membrane or mucosal membrane grafts]. / Unterlidsrekonstruktion von traumatisch bedingten Narbenentropien mittels Amnionmembran- oder Mundschleimhauttransplantation.

BACKGROUND: A retrospective evaluation was undertaken of eyelid reconstruction with amniotic membrane or oral mucosal membrane transplantation in patients with lower lid cicatricial entropion after orbital surgery. PATIENTS AND METHODS: Seven patients (four women) were treated with a scar tissue dissection and an amniotic membrane or mucosal membrane transplantation between 2003 and 2006 (Five amniotic membrane grafts and two oral mucosal membrane grafts). In selected cases additional procedures like a lateral tarsal strip operation, a tarsal fracture, or the reinsertion of the lower lid retractors were performed. RESULTS: All patients showed a favourable postoperative result with a good anatomic correction of the entropion and a regression of the preoperative disturbances. All the grafts took well. Two patients had to be reoperated twice and one patient three times as a result of a relapse of the cicatricial entropion. However, as well in these patients the anatomical and functional result was favourable at the end. CONCLUSIONS: The difficult scar dissection with the subsequent amniotic membrane or oral mucosal membrane transplantation seems to be an appropriate procedure to reconstruct complicated cicatricial entropion after orbital surgery.

Assessment of ocular transduction using single-stranded and self-complementary recombinant adeno-associated virus serotype 2/8.

To date adeno-associated viral (AAV) vectors are the only gene therapy vectors that have been shown to efficiently transduce photoreceptor cells and have thus become the most commonly used vector for ocular transduction. Various AAV serotypes have been evaluated in the eye, the first of which was AAV2, which is able to transduce photoreceptors, retinal pigment epithelium (RPE) and retinal ganglion cells. AAV serotypes 1 and 4, as well as AAV2 pseudotyped with these capsids, only transduce the RPE. AAV serotype 5 and AAV2/5 transduce the photoreceptors as well as RPE, but not retinal ganglion cells. Here, we assessed the capacity of the novel serotype AAV2/8 to transduce various ocular tissues of the adult murine retina by administering AAV2/8 green fluorescent protein intravitreally, subretinally and intracamerally. We also determined the kinetics and efficiency of self-complementary AAV (scAAV) vectors of serotypes 2/2, 2/5 and 2/8 and compared them with single-stranded AAV (ssAAV). We found that ssAAV2/8 transduces photoreceptors and RPE more efficiently than ssAAV2/2 and ssAAV2/5, and that scAAV2/8 had faster onset and higher transgene expression than ssAAV2/8. This improved transduction efficiency might facilitate the development of improved gene therapy protocols for inherited retinal degenerations, particularly those caused by defects in photoreceptor-specific genes.

Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation.

AIMS: To characterize genotype, phenotype, and age-related penetrance in a Swiss pedigree with juvenile open-angle glaucoma (JOAG). METHODS: In a large Swiss family with history of glaucoma and 82 living members of four generations, we conducted molecular analysis and a detailed phenotype characterization in 52 family members. Mutation analysis was carried out using single-strand conformation polymorphism and DNA sequence analyses of the suspected candidate gene, myocilin (MYOC). RESULTS: We detected a Gly367Arg mutation in the MYOC gene of 13 family members. Nine of them (69.2%) had glaucoma: mean IOP 35.3 mm Hg, range 24-50 mm Hg; mean age at diagnosis 34.9 years, range 28-51 years. Two mutation carriers were glaucoma suspects, one (age 15) was unaffected, and one (age 16) not available for clinical examinations. Age-related glaucoma penetrance was 50% at 30 and 78% at 40. Untreated IOP resulted in rapid disease progression, whereas good IOP control, usually only by means of filtration surgery, could stabilize the disease. None of the wild-type members had glaucoma. CONCLUSIONS: This Swiss family is the largest reported Gly367Arg pedigree to date. The exact genotype and phenotype characterization allowed a reliable risk and prognosis assessment and targeted eye-care planning for the family. The study demonstrates the importance of genetic investigations in glaucoma families, carrying the potential of long-term socio-economic benefits.

[Amaurosis fugax with elevated acute phase proteins]. / Amaurosis fugax mit erhöhten Akutphasenproteinen.

Case report of a 66-year-old woman with episodes of amaurosis fugax and hemicranic headache with otherwise normal ophthalmologic and neurological examinations and normal imaging. While ESR was in the normal range for patient's age, acute phase proteins (C-reactive protein and fibrinogen) were elevated. Giant cell arteritis was proved by temporal artery biopsy. Giant cell arteritis should be considered as an important differential diagnosis of amaurosis fugax even in patients with normal ESR. Acute phase protein testing can give relevant diagnostic information.

Vitrectomy for juvenile uveitis: prognostic factors for the long-term functional outcome.

PURPOSE: This study evaluated the long-term effect of pars plana vitrectomy (PPV) in children and adolescents with chronic uveitis on visual function, anatomical outcome, and the requirement of systemic treatment. Further, predictive preoperative factors associated with a beneficial visual outcome were assessed. METHODS: Retrospective review of 29 eyes of 23 consecutive paediatric and juvenile patients below 20 years of age with chronic uveitis who underwent a PPV for visually significant opacities in 25 eyes, vitreous haemorrhage in three eyes, and retinal detachment in one eye. The clinical diagnosis was chronic intermediate uveitis in 22 eyes and retinal vasculitis of different origin in seven eyes. RESULTS: LogMAR visual acuity improved from an average of 0.91 to 0.33 (P<0.001). Cystoid macular oedema (CME) was significantly reduced in eight of 10 eyes postoperatively (P=0.021). In the multiple regression analysis, a low preoperative logMAR visual acuity and the presence of a CME had a negative influence on the final logMAR visual acuity. Furthermore, the appearance of chronic uveitis relapses was significantly reduced from 15 eyes before to seven eyes after surgery (P=0.042). CONCLUSIONS: PPV has a beneficial effect on the course and the complications of chronic uveitis in paediatric and juvenile patients with respect to the anatomical and visual outcome. Preoperative logMAR visual acuity and clinically significant CME were the most accurate predictors for the functional outcome.

[Pars plana vitrectomy for idiopathic vitreous floaters]. / Pars-plana-Vitrektomie bei idiopathischen Glaskörpertrübungen.

BACKGROUND: The aim of this study was to evaluate the role of pars plana vitrectomy (PPV) in patients with persistent vitreous floaters (VF) in phakic (56.7 %) or pseudophakic (43.3 %) eyes. SUBJECTS AND METHODS: A retrospective study of 24 consecutive patients (30 eyes) who underwent a 2-port-PPV using indirect opthalmoscopy between 1992 and 2003 was carried out. Main outcome measures were postoperative visual acuity (PVA), incidence of postoperative complications and patient satisfaction, which has been assessed retrospectively using a detailed questionnaire. RESULTS: Symptoms resolved in all patients. PVA was significantly better (0.91 +/- 0.2 vs. 0.84 +/- 0.2 preoperative visual acuity) or equal in 25 patients (83.3 %). One pseudophakic patient (3.3 %) experienced a retinal detachment 48 months after surgery. In 5 of 17 phakic eyes (35 %) a cataract extraction had to be performed during the follow-up period. All patients were satisfied with their overall visual function. DISCUSSION: This study shows PPV to be a safe and effective primary treatment for visually disturbing VF. In spite of the small number of cases with a lower PVA (5 eyes/16.7 %), which in the most severe case corresponded to a reduction of VA from 1.0 to 0.6 due to a nuclear sclerosis of the lens, all patients were satisfied. As vitreoretinal complications may occur, a critical patient selection and a careful preoperative assessment of specific risks of vitrectomy are mandatory.

Effect of steroidal and non-steroidal drugs on the microglia activation pattern and the course of degeneration in the retinal degeneration slow mouse.

BACKGROUND: In hereditary retinal degeneration, microglia cells become activated, migrate through the outer nuclear layer (ONL) and accumulate in the subretinal space. Although this inflammatory process is not likely to be responsible for the onset of photoreceptor apoptosis, cytotoxic substances secreted by activated microglia could potentially accelerate and perpetuate the degenerative process. Anti-inflammatory drugs have been shown to modulate the microglia response in neurodegenerative disorders and potentially ameliorate the disease progression in various animal model systems. In this study we wanted to test the impact of the most commonly used anti-inflammatory drugs (acetylsalicylate and prednisolone) on the microglia activation pattern, the rate of caspase-3-dependent photoreceptor apoptosis and the course of the degeneration in the retinal degeneration slow (rds) mouse retina. METHODS: 169 pigmented rds mice and 30 CBA wild-type mice were used for this study. The treatment groups were injected daily with either acetylsalicylate (200 mg/kg) or prednisolone (2 mg/kg) i.p. from day 0 up to 3 months. Animals were sacrificed at days 10, 14, 16, 18, 20, 30, 40, 60 and 90. Cryoprotected frozen sections were immunostained with F4/80 and cleaved caspase-3 antibodies. The main outcome measures were the total microglia count in the subretinal space, the total cleaved caspase-3-positive cells in the ONL and the averaged number of photoreceptor rows in the midperipheral retina. RESULTS: Neither acetylsalicylate nor prednisolone reduced subretinal microglia accumulation in the rds mouse degeneration model. Moreover, they aggravated migration and accumulation in the early time course. The apoptotic cascade started earlier and was more pronounced in both treatment groups compared to the control group. The pace of retinal degeneration was not reduced in the treatment groups compared to the untreated control. In contrast, acetylsalicylate did significantly accelerate the photoreceptor cell degeneration in comparison to the prednisolone (p < 0.001) and to the control group (p < 0.001). CONCLUSIONS: Acetylsalicylate and prednisolone do not decrease the microglia response in the rds mouse and are not neuroprotective. More research is needed to clarify the molecular mechanisms which lead to photoreceptor cell death and to elucidate the complex role of microglia in inherited retinal degeneration.

[First experience with amniotic membrane transplantation]. / Erste Erfahrungen mit Amnionmembrantransplantationen.

BACKGROUND: The purpose of this retrospective study was to analyze the outcome of amniotic membrane transplantation (AMT) performed at the University Eye Clinic Bern during the last 12 months. PATIENTS AND METHODS: Nine men (62.4 +/- 16.7 yrs.) and four women (78.3 +/- 22.3 yrs.) were treated with an AMT and grouped according to the ophthalmologic diagnosis: Group A, chronic corneal surface defect without limbal stem cell deficiency (n = 8); Group B, conjunctival fornix reconstruction (n = 7); Group C, filtering bleb defect (n = 2). RESULTS: 11/17 (65 %) AMT's performed in 14 eyes of 13 patients showed a favorable postoperative result after a mean follow-up time of 8.7 (+/- 2.9) months. In Group A (chronic corneal surface defect) 4/8, in Group B (conjunctival fornix defect) 7/7 and in Group C (filtering bleb defect) 0/2 showed an improvement of the basic ocular problem. 4/8 patients from Group A and 7/7 patients of Group B showed postoperatively a strong reduction of the ocular inflammation. CONCLUSIONS: In the present small study, favorable results were achieved in patients with chronic corneal surface defects without limbal stem cell deficiency and conjunctival fornix defects following AMT. In patients with fornix defects, the AMT seemed to be a valuable alternative to the more complicated transplantation of mouth- or nose mucous membrane. The two eyes with filtering defects failed.