Policy implications of regional variations in eye disease detection and treatment on Prince Edward Island: a repeated cross-sectional analysis, 2010-2012.

BACKGROUND: In Canada, government insurance covers eye care services provided by ophthalmologists and other physicians. However, government coverage for services provided by optometrists, non-medical school trained primary eye care providers, varies regionally. Little is known about the impact of a funding model in which ophthalmologist services are government-insured but services provided by optometrists are not, on eye care utilization and eye disease detection and treatment. We aimed to address this question by examining geographic variations in eye care service utilization on Prince Edward Island (PEI). METHODS: PEI physician-billing data from 2010 to 2012 was analyzed across five distinct geographic regions (Charlottetown, Summerside, Prince, Queens & Kings and Stratford). The residential location of patients and practice locations of eye care providers were identified using the first three digits of their respective postal code. Age-standardized rates were computed for comparisons across different regions. RESULTS: There were six ophthalmologists practicing on PEI, five with offices in Charlottetown. Twenty optometrists practiced on the island with offices across the province. Stratford is closest and Prince farthest from Charlottetown. Age-standardized utilization rates of ophthalmologists per 100 populations were 10.44 in Charlottetown and 10.90 in Stratford, which was significantly higher than in other regions (7.74-8.92; p < 0.05). The disparities were most pronounced amongst the elderly. The prevalence of glaucoma visits was higher in Charlottetown (6.10%) and Stratford (6.38%) and lower in other regions. A similar pattern was observed for the prevalence of cataract visits. While the prevalence of diabetes visits was higher in Prince and Summerside, the utilization of ophthalmologists by people with diabetes was almost twice as high in Charlottetown (6.49%) than in Prince (3.88%). CONCLUSIONS: The observed discrepancies in vision care utilization across geographic regions were likely attributed to barriers in accessing government-insured, geographically concentrated ophthalmologists, as opposed to a reflection of the true differences in eye disease occurrence. The lower prevalence of glaucoma visits in regions farther away from ophthalmologist offices may result in delayed detection and blindness in this population. Encouraging ophthalmologists to work in other areas of the province and/or to publicly fund services provided by optometrists may mitigate the observed disparities. TRIAL REGISTRATION: Not applicable.

Prevalence of factor V Leiden and activated protein C resistance in central retinal vein occlusion.

PURPOSE: Factor V Leiden is a common inherited mutation that is a significant risk factor for deep vein thrombosis. It results in resistance to activated protein C (APC). The association between factor V Leiden and central retinal vein occlusion (CRVO) remains controversial. This study was designed to determine the prevalence of APC resistance and the factor V Leiden mutation in patients with CRVO in a controlled study. METHODS: The study was designed as a case control study conducted in a tertiary care retina practice. The prevalence of APC resistance and factor V Leiden was determined by genetic testing of blood samples obtained from patients with CRVO and clinic control patients. RESULTS: Factor V Leiden was identified in 2.3% of patients with CRVO and 3.5% of clinic control patients. There was no significant association between the presence of factor V Leiden and CRVO (odds ratio, 1.13; 95% confidence interval, 0.65-1.98; P = 0.66). CONCLUSION: Factor V Leiden does not appear to be associated with CRVO. Routine screening of patients with CRVO does not appear to be warranted.

Evaluation of a hand-held autorefractor in children younger than 6.

PURPOSE: To evaluate a hand-held portable autorefractor in a pediatric population and compare results with those found on retinoscopy by experienced pediatric retinoscopists. METHODS: One-hundred and two children aged 5 to 72 months were examined with and without cycloplegia using an autorefractor, and the results compared with those found on standard retinoscopy by two ophthalmologists masked as to the autorefractor findings. Results were converted from conventional notation using plus cylinder to the h-space notation and compared in three-dimensional h-space. RESULTS: There was remarkable agreement between the results found by autorefraction and manual retinoscopy using loose lenses or a phoropter. The findings were similar both for sphere and cylinder across the age ranges studied. CONCLUSIONS: The Nikon Retinomax is an accurate instrument to estimate refractive error in children younger than 6 and could prove useful in the office, the operating room, or as a screening device.

Ocular allergic disease.

Ocular allergy is a common condition that usually affects the conjunctiva of the eye and is therefore often referred to as allergic conjunctivitis. The severity of the disease can range from mild itching and redness, as seen in seasonal allergic conjunctivitis, to the more serious vision threatening forms of ocular allergy which affect the cornea, such as atopic keratoconjunctivitis. The pathogenesis of allergic conjunctivitis involves a complex mechanism which centers around IgE-mediated mast cell degranulation and release of multiple preformed and newly formed inflammatory mediators. The diagnosis of allergic conjunctivitis is usually a clinical one which can be made based on a thorough history and careful examination. Treatment of ocular allergy should begin with conservative measures including allergen avoidance, environmental control, ocular irrigation and cold compresses. Pharmacotherapy of allergic conjunctivitis consists of several classes of drugs. Antihistamines are widely used to treat mild conditions such as seasonal and perennial conjunctivitis and potent new agents such as levocabastine and emedastine are now available. Mast cell stabilizers such as sodium cromoglycate are both safe and effective and are commonly used in ocular allergy. More effective mast cell stabilizers such as nedocromil, lodoxamide and olopatadine are now being used. Nonsteroidal antiinflammatory drugs have demonstrated only limited efficacy and, as such, are not widely used. Topical steroids are very effective in treating signs and symptoms but are reserved for only refractory cases due to their serious side effects. Loteprednol and rimexelone are newer corticosteroids which reportedly have less of an effect on intraocular pressure. Cyclosporine has recently been shown to be highly effective in cases of vernal keratoconjunctivitis and atopic keratoconjunctivitis while producing no adverse effects.

Kynurenic acid-induced protection of neurochemical and behavioural deficits produced by quinolinic acid injections into the nucleus basalis of rats.

Injection of the endogenous tryptophan metabolite, quinolinic acid (120 nmol in 1.0 microliter) unilaterally into the basal forebrain of rats resulted in a significant ipsilateral decrease in cortical choline acetyltransferase activity, suggesting that cholinergic cells of the nucleus basalis magnocellularis (nbm) were damaged. Injected animals also showed a significant deficit in performance on an 8-arm radial maze, compared to sham operated controls, indicating an impairment of memory. Co-injection of another endogenous tryptophan metabolite, kynurenic acid (360 nmol in 1.0 microliter) with quinolinic acid afforded an almost complete protection against the neurotoxic and memory-impairing effects of quinolinic acid alone. These findings support previous reports that kynurenic acid can protect against the neurotoxic effects of quinolinic acid and indicate for the first time that kynurenic acid can also protect against impairments of memory produced by injection of quinolinic acid into the nbm.

Effects of scopolamine and unilateral lesions of the basal forebrain on T-maze spatial discrimination and alternation in rats.

Cholinergic systems are thought to play a role in memory. It has been suggested that cholinergic neurons, possibly the cortically projecting cells of the nucleus basalis magnocellularis, are differentially involved in working and reference memory. To evaluate this hypothesis the effects on memory of scopolamine (0, 0.3, 0.6 mg/kg) or unilateral kainic acid (4.7 nmoles in 1 microliter) lesions of the basal forebrain of rats were tested. Working memory, the recall of recent events of transient importance that is vulnerable to interference, was tested using a T-maze alternation task; reference memory, information stored over the long term that is relatively resistant to interference, was evaluated using a spatial discrimination task in the T-maze. The differential sensitivity of the two tasks to interference effects was confirmed by the finding that the insertion of a 30-sec delay between trials significantly reduced performance in the alternation but not the spatial discrimination task. Furthermore, scopolamine or the lesions significantly impaired alternation but not spatial discrimination performance. Biochemical assays of the kainate-injected brains confirmed that the cortical cholinergic marker, choline acetyltransferase, was significantly reduced. These results support the hypothesis that working and reference memory may be differentially controlled by cholinergic systems.

The neurotoxic actions of quinolinic acid in the central nervous system.

Excitotoxins such as kainic acid, ibotenic acid, and quinolinic acid are a group of molecules structurally related to glutamate or aspartate. They are capable of exciting neurons and producing axon sparing neuronal degeneration. Quinolinic acid (QUIN), an endogenous metabolite of the amino acid, tryptophan, has been detected in brain and its concentration increases with age. The content of QUIN in the brain and the activity of the enzymes involved in its synthesis and metabolism show a regional distribution. The neuroexcitatory action of QUIN is antagonized by magnesium (Mg2+) and the aminophosphonates, proposed N-methyl-D-aspartate (NMDA) receptor antagonists, suggesting that QUIN acts at the Mg2+ -sensitive NMDA receptor. Like its excitatory effects, QUIN's neurotoxic actions in the striatum are antagonized by the aminophosphonates. This suggests that QUIN neurotoxicity involves the NMDA receptor and (or) another receptor sensitive to the aminophosphonates. The neuroexcitatory and neurotoxic effects of QUIN are antagonized by kynurenic acid (KYN), another metabolite of tryptophan. QUIN toxicity is dependent on excitatory amino acid afferents and shows a regional variation in the brain. Local injection of QUIN into the nucleus basalis magnocellularis (NBM) results in a dose-dependent reduction in cortical cholinergic markers including the evoked release of acetylcholine. A significant reduction in cortical cholinergic function is maintained over a 3-month period. Coinjection of an equimolar ratio of QUIN and KYN into the NBM results in complete protection against QUIN-induced neurodegeneration and decreases in cortical cholinergic markers. In contrast, focal injections of QUIN into the frontoparietal cortex do not alter cortical cholinergic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of altered cholinergic function on working and reference memory in the rat.

Many data suggest that the brain's cholinergic neurons participate in the control of memory and it has been suggested that cholinergic systems are involved differentially in working and reference memory. To test this hypothesis the effects on memory of unilateral injections of the neurotoxins, quinolinic acid or kainic acid into the cortically projecting cholinergic cells of the nucleus basalis magnocellularis (nbm) were evaluated. In experiment 1, quinolinate-injected (n = 7) and sham-operated (n = 7) rats were tested in a T-maze alternation task that requires working memory. Lesion rats performed significantly more poorly than shams and subsequent biochemical assays of cortical choline acetyltransferase (CAT) activity revealed significant reductions in the lesion rats. In experiment 2, kainate-injected (n = 9) and sham-operated (n = 8) rats were trained in an eight-arm radial maze with only four arms baited. Lesion rats made significantly more working memory errors (entries into baited arms from which the food had already been collected) than reference memory errors (entries into never baited arms). CAT assays showed that the lesion led to a decrease in cortical CAT with no significant change in hippocampal CAT. The results of these studies support the hypothesis that cholinergic neurons of the basocortical system may be differentially involved in working and reference memory.

Functional and neurochemical cortical cholinergic impairment following neurotoxic lesions of the nucleus basalis magnocellularis in the rat.

The effect of kainic and quinolinic acid on cortical cholinergic function was examined following injections of these agents into the nucleus basalis magnocellularis (nbm) or into the frontoparietal cortex. The release of cortical 3H-acetylcholine (3H-ACh), high affinity choline uptake (HACU) and acetylcholinesterase was measured 7 days following injections of saline (control), kainic acid (4.7 nmoles) and quinolinic acid (60, 150 and 300 nmoles) into the nbm. These cortical cholinergic parameters were also examined after injections of saline (control), kainic acid (9.4 nmoles) and quinolinic acid (300 nmoles) into the fronto-parietal cortex. The release of 3H-ACh, HACU and AChE was significantly reduced in animals injected with kainic or quinolinic acid into the nbm. Histological examination of stained sections showed a loss of cell bodies in the region of the nbm and the globus pallidus. The size of the lesion produced by quinolinic acid was proportional to the dose injected into the nbm. In animals injected with kainic acid or quinolinic acid into the cerebral cortex, the release of 3H-ACh, HACU and AChE was not significantly reduced when compared with control animals, although histological examination of stained cortical sections showed a marked loss of cortical neurons. The results show that quinolinic acid, an endogenous neuroexcitant, produces a deficit of cholinergic function similar to that described in the cortical tissue of patients with senile dementia of Alzheimer's type. The toxic effects of quinolinic acid on cortical cholinergic function are due to its action on cholinergic cell bodies in the nbm.(ABSTRACT TRUNCATED AT 250 WORDS)

Quinolinic acid neurotoxicity in the nucleus basalis antagonized by kynurenic acid.

Quinolinic acid, a metabolite of tryptophan, behaves as an excitotoxic amino acid. It has been proposed that quinolinic acid might be implicated in neurodegenerative diseases. The related metabolite, kynurenic acid, has been found to be a powerful antagonist of quinolinic acid. The ability of quinolinic acid, alone or in combination with kynurenic acid, to destroy cholinergic neurons projecting to the cortex was examined by morphological and biochemical criteria. The compounds were injected unilaterally into the nbm of the rat. Neuronal destruction of the basal forebrain occurred with quinolinic acid alone; however, no cell loss was observed when kynurenic and quinolinic acid were co-injected. Quinolinic acid lesions of the nucleus basalis caused significant decreases in cortical choline acetyltransferase, acetylcholinesterase, high affinity choline uptake and 3H-acetylcholine release. These reductions in cortical cholinergic markers were prevented by co-injecting kynurenic with quinolinic acid. A significant decrease in cortical choline acetyltransferase activity was observed three months following quinolinic acid lesions of the nucleus basalis. The results indicate that quinolinic acid can be used as an endogenous neurotoxin to produce lesions of the nbm resulting in impaired cortical cholinergic function similar to that seen in Alzheimer's disease.

Differential effects of scopolamine on working and reference memory of rats in the radial maze.

Anticholinergics have often been found to impair choice accuracy in the radial maze. Some researchers have suggested that this indicates involvement of cholinergically innervated structures in cognitive mapping while others argue that these structures mediate working memory. However, most results are open to either interpretation since the baiting method did not allow a distinction between reference and working memory errors. To further test these hypotheses this study examined the effects of systemic scopolamine on radial maze performance, using a 4-out-of-8 baiting procedure. Food-deprived Wistar rats were pretrained until working memory choice accuracy stabilized to a criterion of 87% or better. Scopolamine (0.1, 0.4 and 0.8 mg/kg, IP, 30 min before a session) significantly increased the number of working memory errors (re-entries into baited arms) whereas reference memory errors (entries into never baited arms) did not change significantly. Observed deficits appeared not to be attributable to a drug-induced disruption of motivational systems. Results confirm the behavioural similarities between the memorial effects of hippocampectomy and anticholinergics, and implicate cholinergically innervated structures in working memory.