Neuroglobin gene therapy prevents optic atrophy and preserves durably visual function in Harlequin mice.

Neuroglobin (NGB) is considered as an endogenous neuroprotective molecule against stroke, since the protein alleviates the adverse effects of hypoxic and ischemic insults. We previously demonstrated the functional link between NGB and mitochondria since it is required for respiratory chain function. Thus, here, we evaluated the relevance of this effect in the Harlequin (Hq) mouse strain, which exhibits retinal ganglion cell (RGC) loss and optic atrophy due to a respiratory chain complex I (CI) defect. A twofold decrease of NGB amounts was observed in Hq retinas. We constructed a recombinant adeno-associated virus which combines to the mouse NGB open reading frame, its 5' and 3'UTR, for guarantying mRNA stability and translation capacity. The vector was administrated intravitreally to Hq mice and NGB expression was stable for up to 7 months without negative effect on retinal architecture or function. On the contrary, RGCs and their axons were substantially preserved from degeneration; consequently, CI activity in optic nerves was protected conferring improvements in vision. Hence, we established that NGB prevents respiratory chain impairment, therefore, protecting visual function otherwise compromised by mitochondrial energetic failure.

Correlation between peripapillary atrophy and corticosteroid therapy in patients with Vogt-Koyanagi-Harada disease.

AIMS: To determine the correlation between systemic corticosteroid therapy and the occurrence and size of peripapillary atrophy (PPA) in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: All patients with VKH disease were retrospectively reviewed for their corticosteroid regimen. The extent of the PPA, if present, was measured using digitized imaging software, by two masked observers. Eyes with myopia greater than 6 dioptres or glaucoma were excluded. The patients were classified into three groups: early high (EH), late high (LH), and low dose (LD), according to the dose and timing of corticosteroids received during the acute phase of the disease. RESULTS: There were 40 eyes in the EH group, 25 eyes in the LH group, and 23 eyes in the LD group. Multivariate analysis showed that corticosteroid therapy was the main determinant of PPA occurrence. All the eyes in the LD group had PPA and eyes in the LH groups were 4.02 times (95% confidence interval 1.24-13.07) more likely to develop PPA than those in the EH group. The LD group also had larger PPA to disc ratios than the EH group. (Mean of 2.83 vs0.19, P<0.001). CONCLUSION: The development and extent of PPA in patients with VKH disease appear to be dependent on the dose and timing of systemic corticosteroids.

[Results of the "Ocular hypertension treatment study"]. / Ergebnisse der "Ocular hypertension treatment study" (OHTS).

Ocular hypertension (OHT) is defined as intraocular pressure (IOP) elevated above normal levels which occurs without detectable damage to the papilla or visual field. It is considered to be the most important risk factor for developing primary open-angle glaucoma (POAG). The "Ocular hypertension treatment study" (OHTS) addresses the issue of whether lowering IOC before damage to the papilla or visual field occurs can hinder their development and whether OHT can be treated categorically. This randomized, prospective, nonmasked and non-placebo-controlled, multicenter study documents the protective effect of prophylactic lowering of IOC and identifies and explains the risk factors for developing POAG. These include advancing age, reduced corneal thickness, increased pattern standard deviations in white-on-white perimetry, and elevated vertical or horizontal cup to disc ratio. Due to the large individual differences in risk distribution and the very high costs of treating OHT, the question of whether OHT should be treated on principle remains open in the OHTS. This decision must be made on an individual basis after each patient's risk has been assessed.

[Results of the Collaborative Initial Glaucoma Treatment Study (CIGTS)]. / Ergebnisse der "Collaborative Initial Glaucoma Treatment Study" (CIGTS).

The Collaborative Initial Glaucoma Treatment Study (CIGTS) was initiated to evaluate whether local medical therapy or trabeculectomy is the better initial treatment for patients with newly diagnosed open-angle glaucoma. Visual field progression, intraocular pressure, and visual acuity were to be monitored for a period of 5 years. A total of 607 patients were randomly distributed among the two groups and controlled at 6-month intervals. At the same time the investigators tried to record quality of life using a questionnaire. Both trabeculectomy and medical therapy were able to lower intraocular pressure significantly, whereas trabeculectomy was more effective. The results of the questionnaire showed only minor differences between the two groups. The medically treated patients reported slightly more ocular symptoms than the patients in the trabeculectomy group.

Reversal of optic canal stenosis in osteopetrosis after bone marrow transplant.

PURPOSE: To describe a patient with infantile osteopetrosis and optic atrophy secondary to optic canal stenosis who demonstrated optic canal enlargement after bone marrow transplant. METHODS: Case report. A 3-month-old infant with infantile "malignant" osteopetrosis underwent ophthalmic examination, including visual evoked potentials, electroretinogram, and computed tomography (CT). Bone marrow transplant was performed at 8 months of age. RESULTS: Examination revealed visual loss and optic atrophy, left eye greater than right eye, secondary to optic canal stenosis. Flash visual evoked potentials revealed a normal waveform in both eyes with increased latency in the left eye. Electroretinogram was normal in both eyes. CT after bone marrow transplant showed enlargement of the optic canals. Vision remains stable 43 months after bone marrow transplant. CONCLUSIONS: Bone marrow transplant in infantile osteopetrosis may be followed by reversal of optic canal stenosis and preservation of vision.

Vitreopapillary traction in proliferative diabetic vitreoretinopathy [ssee comments].

AIM: To present the clinical profile of a new entity in advanced proliferative diabetic vitreoretinopathy (PDVR). Mechanisms of vision loss due to vitreopapillary traction on the nasal optic disc are described, followed by an introduction of methods for prevention and treatment in such cases. METHODS: 17 patients with PDVR and traction on the nasal side of the optic disc, pallor of the optic nerve head, and reduced visual acuity were included in the study. Six patients were observed retrospectively and 11 patients prospectively before and after pars plana vitrectomy. Pre- and postoperative examinations included visual acuity, Goldmann's visual field, fluorescein angiography, and measurements of visual evoked potentials (VEP). RESULTS: During a postoperative follow up period of 3 to 24.5 months (mean 14.5 months) an improvement in optic disc appearance combined with an increased visual acuity (mean increase in VA = 0.171) was observed in 15/17 (88.3%) patients. In addition, 8/17 (47%) of these patients showed higher VEP amplitudes (mean 3.83 microV), and eight (6/8 of the same patients as VEP amplitudes) patients showed a reduction of latency (mean reduction 22.25 ms) during VEP assessment. CONCLUSION: These results suggest that vitreopapillary traction may damage the anterior optic nerve, via decreased axoplasmatic flow in the optic nerve fibres and/or mechanical reduction of perfusion in the posterior ciliary arteries. The effects of each mechanism appear to be reversible, but in the long term might lead to irreversible optic nerve atrophy. Therefore, in patients with vitreopapillary traction, early vitrectomy should be considered as a method to prevent optic neuropathy.

Glaucomatous neurodegeneration and the concept of neuroprotection.

Glaucomatous neurodegeneration is a progressive pathological affair morphologically characterized by RGC death resulting in functional visual deterioration. Although a variety of primary insults ranging from mechanical trauma to ischemia to genetic susceptibility can initiate disease onset, apparently loss of trophic support and excitotoxin release remain the common themes responsible for neuronal damage and eventual cell death by apoptosis. The spread of this damage is perpetuated by secondary degeneration that allows directly injured neurons to release noxious and degenerative substances into the surrounding cells. Neuroprotection is a collective therapeutic approach the aim of which is to provide resilience to such neurons in an effort to prevent or delay progressive neuronal degeneration. At present, definitive neuroprotective therapy remains unachieved despite a variety of approaches having been defined and intensely pursued. However, the evolution in our understanding of glaucoma continues to offer reason for optimism. To this end, we remain unreservedly hopeful in the labor and committed work of dedicated investigators. We are all indebted to them.

The use of dexamethasone in preventing ocular complications in tuberculous meningitis.

Twenty-seven patients with tuberculous meningitis (TBM) were treated with ethambutol, isonicotinic acid hydrazide, streptomycin and dexamethasone and 28 were treated with triple anti-tuberculous drugs only. Only two of the patients to whom steroids were given developed ocular complications as compared to seven of those not receiving dexamethasone. High dose dexamethasone apparently prevents optic atrophy in TBM. Controlled double-blind studies with and without dexamethasone are needed to confirm this postulation.

[Osteitis deformans cranio-orbitalis (Paget's) in a young patient. Operation and clinico-pathology study (author's transl)]. / Eine deformierende kranioorbitale Ostitis (Paget bei einer jungen Patientin (Operation und klinisch-pathologische Studien).

Among the cranio-facial anomalies involving the orbit, Paget's disease is of particular interest due to its progressive evolution and clinico-pathological characteristics. In this article a case of Paget's disease (juvenile type) with orbital expansion in a young woman of 27 years is presented. The onset of clinical symptoms were recorded at the age of 15 years progressing to optic atrophy and blindness in one eye and visual deterioration on the other. The peculiarity of this case lies on the early onset of clinical symptoms due to elective in volvement of the skull and sparing of the facial bones. The surgical decompression (removal of the roof of the orbit and upper wall of the stenosed optic canal) was successful in controlling the evolution to optic nerve atrophy in the seeing eye.