No relationship between socioeconomic status, education level and development and progression of diabetic retinopathy in type 2 diabetes: a FIELD trial substudy.

In 6002 Australian adults with type 2 diabetes and a median 5-year follow-up in the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial, baseline socioeconomic status (SES) and self-reported education level were not related to development of on-trial sight-threatening diabetic retinopathy. Similarly, in a retinal photography substudy (n = 549), two-step diabetic retinopathy progression was not related to SES or education.

Fenofibrate, which reduces risk of sight-threatening diabetic retinopathy in type 2 diabetes, is associated with early narrowing of retinal venules: a FIELD trial substudy.

Retinal vessel calibre metrics were evaluated at baseline and 2 years in a FIELD substudy (n = 208). Central retinal venule calibre was significantly reduced by fenofibrate and unchanged by placebo. Arteriole metrics did not change. Larger studies relating retinal vessel calibre to future diabetes complications and response to therapy are merited.

Retinopathy risk calculators in the prediction of sight-threatening diabetic retinopathy in type 2 diabetes: A FIELD substudy.

AIMS: To evaluate the risk algorithm by Aspelund et al. for predicting sight-threatening diabetic retinopathy (STDR) in Type 2 diabetes (T2D), and to develop a new STDR prediction model. METHODS: The Aspelund et al. algorithm was used to calculate STDR risk from baseline variables in 1012 participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) ophthalmological substudy, compared to on-trial STDR status, and receiver operating characteristic analysis performed. Using multivariable logistic regression, traditional risk factors and fenofibrate allocation as STDR predictors were evaluated, with bootstrap-based optimism-adjusted estimates of predictive performance calculated. RESULTS: STDR developed in 28 participants. The Aspelund et al. algorithm predicted STDR at 2- and 5-years with area under the curve (AUC) 0.86 (95% CI 0.77-0.94) and 0.86 (0.81-0.92), respectively. In the second model STDR risk factors were any DR at baseline (OR 24.0 [95% CI 5.53-104]), HbA1c (OR 1.95 [1.43-2.64]) and male sex (OR 4.34 [1.32-14.3]), while fenofibrate (OR 0.13 [0.05-0.38]) was protective. This model had excellent discriminatory ability (AUC = 0.89). CONCLUSIONS: The algorithm by Aspelund et al. predicts STDR well in the FIELD ophthalmology substudy. Logistic regression analysis found DR at baseline, male sex, and HbA1c were predictive of STDR and, fenofibrate was protective.

Axonal loss and myelin in early ON loss in postacute optic neuritis.

OBJECTIVE: To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual-evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis. METHOD: Thirty-two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging. RESULTS: Although there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = -0.66). INTERPRETATION: Although our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss.

Electrophysiological evidence for heterogeneity of lesions in optic neuritis.

PURPOSE: To examine the natural history of multifocal visual evoked potentials (mfVEPs) within 12 months of the first episode of optic neuritis (ON) in patients with possible multiple sclerosis (MS). METHODS: Twenty-seven patients with a first episode of ON, no previous demyelinating events, and MRI lesions consistent with demyelination were examined with mfVEP. Changes in amplitude and latency of mfVEP were analyzed at 1, 3, 6, and 12 months after an acute attack. RESULTS: Five of 27 patients had persistent loss of amplitude after 12 months of follow-up. This loss was most marked centrally. Amplitude recovered in the remaining 22 patients at 1 month, but delayed latency, which was also most marked centrally, persisted. Of these, two distinct subgroups were identified: six patients with no improvement in latency and 16 patients with significant latency recovery over the 12 months of follow-up, suggesting remyelination. Conversion to MS was highest in the group with severe amplitude loss, followed by the group with no latency recovery. The conversion rate was lowest in the group of patients with latency improvement. CONCLUSIONS: Distinct patterns of disease evolution were identified using mfVEP in patients with first episode of optic neuritis and at high risk for MS, supporting the concept of heterogeneity of early lesions in MS.

Horner syndrome.

Horner syndrome is an uncommon but important clinical entity, representing interruption of the sympathetic pathway to the eye and face. Horner syndrome is almost always diagnosed clinically, though pharmacological testing can be used to confirm the diagnosis. Imaging modalities such as PET, CT and MRI are important components of work-up for patients presenting with acquired Horner syndrome. Our patient's presentation with Horner syndrome unmasked the causative superior sulcus squamous cell carcinoma and a coincidental lower lobe adenocarcinoma. Successful radical treatment of these cancers resulted in complete resolution of the syndrome and disease-free survival at 18 months. We review the anatomy and pathophysiology underlying this and other causes of Horner syndrome.

Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart disease: a 12-month follow-up.

Current stem cell protocols for ischemic heart disease are limited by the small numbers of cells that can be obtained by bone marrow aspirate. To increase myocardial delivery of bone marrow stem cells in patients with chronic ischemic heart disease (CIHD), we used granulocyte colony stimulating factor (G-CSF) for bone marrow mobilization of CD34+ cells, enabling intracoronary infusion of large numbers of CD34+ stem cells. Patients with CIHD (n = 5) demonstrated significantly reduced numbers of CD34+ cells mobilized by G-CSF in comparison to age-matched controls. Sustained reduction in anginal symptoms and improvement in quality of life scores was seen in all patients following infusion of cells. Moreover, mean collateral flow grade at 12-month follow-up angiography significantly improved, indicating sustained myocardial neovascularization. No proliferative retinopathy was induced and no in-stent restenosis seen. However, in two patients with documented increase in collateral flow, complications arose, one developing an acute coronary syndrome and the other a lentigo maligna. These results demonstrate the feasibility of G-CSF mobilization, leukapheresis and intracoronary transfer of CD34+ stem cells in patients with CIHD, but longer-term studies are required to ensure that this protocol is safe and effective.

A case of biopsy-negative temporal arteritis--diagnostic challenges.

A patient with systemic symptoms but no visual loss was investigated for suspected giant cell arteritis. Initial temporal artery biopsy was reported as negative; however, she returned with visual loss 2 months later, and the diagnosis of giant cell arteritis was confirmed with a subsequent biopsy. In hindsight, signs suggestive of the disease were present in the original biopsy, although the usual diagnostic features were absent.

Use of high-dose botulinum A toxin in benign essential blepharospasm: is too high too much?

BACKGROUND: Botulinum toxin (Botox) is the mainstay treatment for benign essential blepharospasm. Current treatment practice appears restricted by several reports demonstrating adverse effects and resistance to high-frequency, higher-dose therapy. This study aimed to explore whether high-dose, high-frequency treatments could be used without developing secondary resistance and without significant side-effects in patients refractory to conventional Botox doses. METHODS: From a cohort of 120 patients being treated with Botox therapy for benign essential blepharospasm and idiopathic hemifacial spasm, case notes from six patients were retrospectively examined. In these patients, therapy had exceeded the recommended 50 units per side for a duration greater than 12 months and at less than 3 monthly intervals. Patterns in subjective severity grading and percentage of improvement as well as reported side-effects were analysed. RESULTS: All patients described greater than 60% improvement and 0-2 severity grading over a 3- to 15-year period with no evidence of secondary resistance. Side-effects were minor, transient and less frequently reported at higher doses. CONCLUSION: In a select group of patients, Botox therapy can be used effectively at doses higher than recommended over long periods with minimal side-effects and little evidence of secondary resistance.

Giant cell arteritis presenting with scalp necrosis--the timing of temporal artery biopsy?

Scalp necrosis in patients presenting with clinical features suggestive of giant cell arteritis is rare. The immediate concern is that temporal artery biopsy might further compromise scalp circulation. We report a case of extensive scalp necrosis caused by giant cell arteritis. Temporal artery biopsy performed after 14 days was not associated with any significant damage and still provided florid evidence of the disease. Rapid and complete scalp healing was achieved with aggressive treatment.

Photodynamic therapy in the management of juxtapapillary capillary haemangiomas.

Capillary haemangiomas occurring on or adjacent to the optic disc pose unique therapeutic problems. Their natural history is highly variable, but has a propensity to lead to the development of progressive exudate with marked deterioration in visual acuity, often culminating in retinal detachment and vitreal haemorrhages. On reviewing the literature, no therapeutic modality has demonstrated an efficacy in treating the lesion and providing an acceptable visual acuity result. A case of a 61-year-old man with a left-sided juxtapapillary capillary haemangioma treated with verteporfin photodynamic therapy is described. The patient's visual acuity improved from 6/36 to 6/12 initially, with an appreciable reduction in exudate and lesion size. Subsequent treatments failed to eradicate the lesion, with visual acuity stabilizing at 6/60. With larger cohorts of patients and variable treatment parameters, the true efficacy of photodynamic therapy to treat these lesions may be determined.

Predictors of recurrent ischemic optic neuropathy in giant cell arteritis.

BACKGROUND: The competing interests of preventing recurrent ischemic optic neuropathy (ION) and minimizing medication side effects make corticosteroid dose reduction in giant cell arteritis (GCA) a difficult problem. The authors sought to determine whether any factors were predictive of recurrent ION. METHODS: Retrospective review of the records of 100 consecutive patients with biopsy-proven giant cell arteritis diagnosed in two Australian hospitals between 1988 and 1998. Among 67 patients who met inclusion criteria for ION in GCA, seven patients had recurrent ION. We compared the seven patients with recurrent ION to the 60 patients with nonrecurrent ION in terms of age, gender, mode of corticosteroid delivery, initial visual acuity in the affected eye, prevalence of bilateral ION, initial erythrocyte sedimentation rate (ESR) level, and rate of corticosteroid dose reduction. In the recurrent ION group, we documented the timing of the recurrence in relation to corticosteroid dose, elevation in acute phase reactants, and relapse of systemic symptoms. RESULTS: We found recurrent ION in GCA in 10% of our cohort, higher than has been previously reported. Recurrences, all of which were ipsilateral, occurred from 3 to 36 months (median 8 months) after the initial ION. None of the clinical indicators the authors examined differed between the two groups. Six of seven patients with recurrent ION had elevations in ESR or C-reactive protein or a new headache at the time of ION recurrence, but in only one of these patients were these features recognized as preceding the recurrent ION. One patient had neither an elevation in acute phase reactants nor a relapse in systemic symptoms of GCA at the time of ION recurrence. CONCLUSIONS: Recurrent ION in GCA is difficult to predict. Although elevated acute phase reactants or new systemic symptoms consistent with GCA were present in six (83%) of our patients with ION recurrence, in only one patient (17%) did these events occur with enough lead time to allow caregivers to act preemptively. Thus, even very close monitoring of GCA patients with ION may not predict ION recurrence.

Snowflake degeneration of an intraocular lens.

Snowflake degeneration of intraocular lenses is a recently recognized late postoperative complication of cataract surgery. All known cases reported to date in the literature have involved polymethyl methacrylate (PMMA) lens optic material. Reported herein is an atypical variant of snowflake degeneration of a PMMA posterior chamber intraocular lens in an 81-year-old woman, 7 years post implantation. The aetiology of the atypical late opacification of the intraocular lens is this case is unclear, and no clinical risk factors appear to have been identified.

Review of severe vaso-occlusive retinopathy in systemic lupus erythematosus and the antiphospholipid syndrome: associations, visual outcomes, complications and treatment.

PURPOSE: To discuss the pathogenesis of severe vaso-occlusive retinopathy in systemic lupus erythematosus (SLE), the association with antiphospholipid antibodies, and its implications for management and prognosis. METHODS: An illustrative case history of a woman with SLE and severe vaso-occlusive retinopathy in the presence of antiphospholipid antibodies is presented. A literature review of previously reported cases and previously published data on the topic was performed and forms the basis for discussion. RESULTS: This is a rare form of retinopathy in SLE as distinct from the more common, benign form, being classically a microangiopathy with diffuse capillary non-perfusion and small arterial or arteriolar occlusions in the retina. Poor visual outcomes with visual loss are reported in 80% of cases with neovascularization occurring in 40% of cases. It is associated with antiphospholipid antibodies, typically characterized by microthrombosis and immune complex mediated vasculopathy rather than a true vasculitis. There is a strong association between this severe form of retinopathy and central nervous system manifestations of SLE. Anticoagulation has a role in the secondary prevention of thrombosis in the presence of antiphospholipid antibodies, but the role of aspirin and immunosuppression is unclear in the treatment of this condition. Vigilant ophthalmic follow up and aggressive treatment of neovascularization and vitreous haemorrhage can prevent further visual loss. These points are highlighted in the brief case report presented. CONCLUSION: Severe vaso-occlusive retinopathy is a rare form of retinopathy in SLE often associated with poor visual prognosis and neovascularization. It may be a manifestation of the antiphospholipid syndrome. Treatment is aimed at preventing further thrombosis and complications arising from neovascularization.

Fatigable ptosis and pseudoretraction caused by myasthenia gravis.

The case is presented of a 59-year-old woman with myasthenia gravis. Fatigable ptosis and pseudoretraction caused by the myasthenia gravis are illustrated in a series of clinical photographs.

Optic neuropathy secondary to radiotherapy for nasal melanoma.

Optic neuropathy is a rare but important complication of radiotherapy used in the treatment of cancers of the head and neck, usually resulting in rapidly progressive blindness in one or both eyes. The case is presented of a 77-year-old woman with bilateral optic neuropathy resulting in blindness, secondary to radiotherapy for a melanoma of the nasal cavity. The onset of optic neuropathy occurred 9 months post-radiotherapy, at a cumulative dose of 6000 rad. The left eye was first involved, with the right eye becoming involved within 2 weeks. Despite treatment with oral anticoagulation and high dose intravenous methylprednisolone, there was progressive deterioration resulting in bilateral optic atrophy, with final visual acuities of perception of light in the right eye and no perception of light in the left eye. This case demonstrates that oral anticoagulation was ineffective in the treatment of progressive radiation-induced optic neuropathy.

Recurrent posterior capsular opacification and capsulorhexis contracture after cataract surgery in myotonic dystrophy.

Cataracts are well known to be associated with myotonic dystrophy. Less well known are the phenomena of recurrent posterior capsule opacification and capsulorhexis contracture post cataract surgery. Two cases are described herein of postoperative capsular complications requiring multiple capsulotomies in patients with myotonic dystrophy. It is proposed that a common aetiology may underlie both posterior capsule opacification and capsulorhexis contracture in myotonic dystrophy cases.