Endogenous endophthalmitis: 10-year experience at a tertiary referral centre.

PURPOSE: Endogenous endophthalmitis (EE) is a sight-threatening emergency and the aetiology is often multifactorial. Delayed diagnosis may exacerbate the poor visual prognosis. We describe the management and visual outcomes of EE presenting to a tertiary referral centre. PATIENTS AND METHODS: A prospective consecutive case series of 64 patients presenting with presumed EE from 1997 to 2007 to the Royal Victorian Eye and Ear Hospital were included. All data were collected in a standardized manner. Outcome measures included: visual acuity, microbial profiles, and vitrectomy rate. RESULTS: In total, 64 cases of EE were identified over the study period with a mean age of 57.5 years, and 53.5% were male. Presenting acuities ranged from Snellen 6/6 to no perception of light (NPL). Identifiable risk factors were present in 78.1%, with the majority related to intravenous drug abuse. A 64.1% culture positivity rate was recorded. A vitrectomy rate of 57, 56, and 21% was recorded in documented bacterial, fungal, and no growth cases, respectively. Final Snellen acuities ranged from 6/6 to NPL. A total of 5 out of 64 eyes were enucleated, of which 3 identified Klebsiella species. Better visual outcome was documented in fungal cases. CONCLUSION: EE is a serious ocular condition and has a varied aetiology. Visual outcomes are often poor, irrespective of the method of management. Fungal aetiology often confers a better prognosis, and vitrectomy is advocated for bacterial proven cases.

Vitreous floaters.

Floaters are a common presenting ophthalmic symptom that may accompany sight-threatening disorders. In most cases, they are often secondary to benign, degenerative changes in the vitreous. In this review, we briefly examine the anatomy of the vitreous and describe how degenerative vitreous change contributes to the development of floaters. The causality of floaters in the presence and absence of a posterior vitreous detachment is reviewed, as is the clinical significance of these symptoms and signs in relation to their predictive value for determining the presence of sight-threatening retinal tears and/or detachment. Finally, a brief review of management options for debilitating floaters is presented.

Expression of the p75 neurotrophin receptor by striatal cholinergic neurons following global ischemia in rats is associated with neuronal degeneration.

The induction of the p75 neurotrophin receptor (p75NTR) on striatal cholinergic neurons by global hypoxic-ischemia has been reported to promote neuron survival. We have found, however, while the p75NTR-expressing neurons survive the insult for the first 5 days, subsequently they undergo shrinkage, loss of choline acetyl transferase (ChAT) expression, and more than 96% are eventually lost by 8 days. In contrast ChAT-expressing cells in the surrounding region of the infarction, do not express p75NTR and there is no evidence of neuronal loss. These results suggest the expression of p75NTR on cholinergic interneurons of the rat striatum is associated with delayed neuronal degeneration.

Sphenoid sinus mucocoele presenting as complete ophthalmoplegia.

Sphenoid sinus mucocoeles represent 1% of all paranasal sinus mucocoeles. We describe a case of a sinus mucocoele with an atypical presentation comprising the sudden onset of a complete ophthalmoplegia. There was good recovery following drainage of the mucocoele.

Chronic hypoxemia: effects on developing nitrergic and dopaminergic amacrine cells.

PURPOSE: Very low birth weight and growth-restricted children have visual impairments including reduced contrast sensitivity, a parameter mediated in part by dopaminergic amacrine cells. The origin of these deficits is uncertain. In experimental fetal growth restriction, induced by placental insufficiency, the morphology and number of dopaminergic amacrine cells as identified by tyrosine hydroxylase staining were examined. In addition, the subclass of nitrergic amacrine cells was examined because nitric oxide released from nitric oxide synthase- containing neurons is proposed as a mediator of neurotoxicity and might contribute to the injury of dopaminergic amacrine cells in this situation. METHODS: Fetal sheep were subjected to 20 or 30 days of placental embolization leading to fetal hypoxemia, hypoglycemia, and growth restriction during the last third of gestation (term, approximately 147 days). Retinal tissue was prepared as wholemounts or cryostat sections and analyzed for retinal area, total number, density, somal size and cell process length of amacrine cells immunoreactive for tyrosine hydroxylase or nitric oxide synthase, and widths of retinal layers. Retinas from fetal sheep at 72, 96, 113, and 140 days' gestation and adults were collected for an ontogenetic study of tyrosine hydroxylase-immunoreactive neurons. RESULTS: In growth-restricted fetuses, the number of tyrosine hydroxylase-immunoreactive neurons and the total length of stained processes per cell were significantly reduced compared to control fetuses. The total number of neuronal nitric oxide synthase- containing neurons was not different between growth-restricted and control fetuses. The thickness of the inner retinal layers was reduced in hypoxemia. CONCLUSIONS: There is damage to tyrosine hydroxylase-immunoreactive amacrine cells during fetal chronic placental insufficiency. This damage might be involved in the altered retinal dopaminergic system observed in very low birth weight infants, some of whom are growth-restricted. Furthermore, a differential susceptibility of tyrosine hydroxylase-immunoreactive and neuronal nitric oxide synthase-containing amacrine cells to hypoxemic injury has been demonstrated. These observations add to the current hypothesis that neuronal nitric oxide synthase- containing neurons are resistant to hypoxemic injury and may be involved in mediating some of the neuronal damage that results from hypoxemic insults.

Depletion of nitric oxide synthase-containing neurons in the diabetic retina: reversal by aminoguanidine.

A close association of neuronal nitric oxide synthase-immunoreactive (nNOS-IR) neurons with the retinal vasculature has been reported and it is proposed that activation of these neurons could be the mechanism by which retinal blood flow and metabolism are linked. Further, advanced glycation end products (AGEs) have previously been shown to be increased in the diabetic retina and aminoguanidine (AG), an inhibitor of advanced glycation, has been shown to attenuate the development of AGE accumulation as well as the progression of experimental diabetic retinopathy. This study examined the effects of short (1 and 3 weeks) and long term (32 weeks) diabetes on nNOS-containing neurons of the retina using NADPH diaphorase (NADPHd) histochemistry. In addition, the effect of aminoguanidine (an inhibitor of advanced glycation and NOS) and NG-nitro-L-arginine methyl ester (L-NAME) (a non-selective NOS inhibitor) on retinal nNOS-containing neurons was examined in short and long term control and diabetic rats. In a separate study, the effect of 2,3 diamino-phenazine (NN0028) (an inhibitor of advanced glycation, but not NOS) was examined in short term (3 weeks) diabetic rats. The number of NADPHd-positive neurons per retina was reduced after one week of diabetes and remained decreased in long term diabetic rats, an effect not observed in diabetic rats rendered euglycaemic by intensified insulin treatment. Treatment of diabetic animals with aminoguanidine or NN0028 prevented the depletion in the nNOS-containing neuron number, an effect not reproduced by L-NAME. These studies suggest that the action of AG in restoring the number of nNOS-containing retinal neurons is mediated by the inhibition of AGE formation. The depletion of nNOS-containing neurons may contribute to alterations in the autoregulation of blood flow which occurs in diabetes.

Ageing has a differential effect on nitric oxide synthase-containing and catecholaminergic amacrine cells in the human and rat retina.

In this study, we assessed the effects of normal ageing on the number, distribution, and somal area of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-positive (NADPHd+) and tyrosine hydroxylase-immunoreactive (TH-IR) amacrine cells in human and rat retina. By using a double-labelling immunohistochemical technique, we have shown that these two enzymes are located in separate amacrine cell populations in the human retina. In normal human retinas from organ donors, we have shown that there was no change in the number, somal area, or retinal distribution of NADPHd+ neurons over an age range of 19-89 years. In contrast, there was a significant decrease (P < 0.05) of 52% in the total number of TH-IR neurons in the group aged 65-89 years compared with the group aged 19-64 years. CA1 and CA2 TH-IR neurons were reduced by 44% and 55%, respectively. In young (3 months) and old (2 years) rats, the number of NADPHd+ neurons did not decrease with ageing, but the number of TH-IR neurons was significantly reduced by 21% (P < 0.05). In a companion study on monkey retina, we have shown that a postmortem delay of 12.5 hours between death and fixation results in a decrease of 33% in the number of both NADPHd+ and TH-IR neurons in the retina compared with the number in retinas fixed immediately after death. The findings of this study on the two subsets of amacrine cells, therefore, are likely to demonstrate the consequences of ageing in the retina and might contribute to visual impairment in the elderly.

Nitric oxide synthase immunoreactivity and NADPH diaphorase staining are co-localised in neurons closely associated with the vasculature in rat and human retina.

Nitric oxide synthase (NOS) is widely distributed throughout the nervous system and is found in neurons which produce nitric oxide (NO). In attempting to elucidate the biological roles of NO in neurotransmission, vasodilation, and in neurodegeneration, nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry has been widely used. NADPHd histochemistry and NOS immunoreactivity (NOS-IR) have been assumed to stain the same population of neurons. However, there have been numerous reports which suggest that this may not always be the case, and in all neuronal populations investigated, the coincidence of NOS and NADPHd must be unequivocally demonstrated. We have examined NADPHd histochemistry and NOS immunoreactivity in the human and rat retina and shown that these are 100% co-localised. Further, we have described the morphology of NADPHd and NOS-IR neurons in the human and rat retina and shown a close association of these neurons and their processes to the retinal vasculature. We have taken the NOS-IR to the ultrastructural level and have identified NOS-IR cells in close association with the basal lamina covering endothelial cells and pericytes of the retinal capillaries. We suggest that NO released from these neurons may be involved in the regulation of retinal microcirculation.