Barrett Katz

A Randomized, Controlled Trial of Corticosteroids in the Treatment of Acute Optic Neuritis

Background and Methods. The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period. Results. Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did ...

The Lacrimal System

This volume is designed as a multi-speciality clinical reference on the lacrimal system. The book presents a systematic approach to the evaluation and management of lacrimal disorders and critically assesses both classic techniques and newer developments, such as laser and endoscopic surgery, local anaesthesia, and same-day surgery. The first section of the book provides essential anatomic and physiological information on the lacrimal system. The second section details the methods used in investigation of lacrimal disorders, including clinical assesment, radiologic studies and endoscopy. The third section offers guidelines for management of specific disease entities and traumatic injuries. The fourth section focuses on surgical techniques and anaesthesia.

Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial

Aims: To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). Methods: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. Results: As in years 1 and 2, pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to pegaptanib treatment. Conclusion: The 3-year safety profile of pegaptanib sodium was favourable in patients with NV-AMD.

Diffuse Unilateral Subacute Neuroretinitis: Morphometric, Serologic, and Epidemiologic Support for Baylisascaris as a Causative Agent

PURPOSE Several nematodes have been postulated as etiologic agents in diffuse unilateral subacute neuroretinitis (DUSN), but the cause of this condition remains uncertain. The authors report the first case of DUSN from the western United States (northern California), along with morphometric, serologic, and epidemiologic evidence supporting Baylisascaris procyonis as its cause. METHODS One patient was examined and evaluated for disc edema and transient obscurations of vision. A diagnosis of DUSN was confirmed when a motile nematode was identified within the substance of the patients retina. Morphometric analysis of the nematode was done from projected fundus photographs. Serologic evidence of Baylisascaris infection was suggested by Western blot analysis. A necropsy was done on 12 raccoons from the area. They were examined for evidence of Baylisascaris infection, previously believed to be nonendemic in the region. RESULTS The intraocular nematode measured 1727 x 67 microns, most consistent with Baylisascaris. The patient had considerable exposure to raccoons, and was seropositive for B. procyonis infection on Western blot analysis. Necropsy evaluation showed B. procyonis infection in 8 of 12 raccoons examined from the area. CONCLUSIONS The morphometric, serologic, and epidemiologic findings in this case provide evidence that the raccoon ascarid, B. procyonis, is a cause of the large nematode variant of DUSN.

Fellow Eye Abnormalities in Acute Unilateral Optic Neuritis: Experience of the Optic Neuritis Treatment Trial

BACKGROUND Visual function in the fellow eye at the onset of unilateral optic neuritis has not been systematically evaluated. The authors prospectively determined the prevalence of abnormalities in the fellow eyes of the 448 eligible patients entered into the Optic Neuritis Treatment Trial. METHODS All patients underwent testing of visual acuity, contrast sensitivity, color vision, and visual field, as well as magnetic resonance imaging (MRI) of the brain and a neurologic examination. RESULTS Abnormalities in the fellow eye were found on measurement of visual acuity in 13.8%, contrast sensitivity in 15.4%, color vision in 21.7%, and visual field in 48.0% of patients. The majority of the fellow eye deficits resolved over several months. A higher prevalence of MRI changes consistent with demyelination of the brain was found in patients with a past history of optic neuritis in the fellow eye compared with patients without such a history (P = 0.004). Patients with abnormal fellow eyes but no history of previous optic neuritis were no more likely to have clinical (P = 0.658) or MRI evidence (P = 0.166) of multiple sclerosis than patients with normal fellow eyes. CONCLUSIONS The improvement of many of the visual deficits indicates that visual abnormalities detected in the fellow eye at the onset of symptomatically unilateral optic neuritis may not represent preexisting optic nerve demyelination. Whether the presence of these deficits is predictive of the development of clinical multiple sclerosis cannot be determined at this time.

Intrapapillary and Peripapillary Hemorrhage in Young Patients with Incomplete Posterior Vitreous Detachment: Signs of Vitreopapillary Traction

PURPOSE The authors describe a benign condition characterized by intrapapillary and subretinal peripapillary hemorrhage, incomplete posterior vitreous detachment with persisting attachments to the disc, and preservation of optic nerve function in young patients. METHODS Eight patients 11 to 42 years of age with no or mild symptoms (blur, spot, or smudge) were referred for disc hemorrhage; seven of these patients were Asian. All underwent complete ophthalmologic examination, including detailed slit-lamp microscopy; particular attention was paid to vitreous attachments. RESULTS Superficial hemorrhage occurred predominantly in the superior hemidisc and was often striking in appearance. Subretinal hemorrhage occurred at the superonasal disc margin in six patients and was centered inferonasally in two. Discs were generally small, mildly dysplastic, and tilted; all were mildly elevated. The posterior vitreous body was separated from the retina but remained attached to the disc. Six patients had subtle visual field abnormalities in the involved eye. The hemorrhages resolved without sequelae or impairment of vision. During a 6-month follow-up, no patient progressed to complete vitreous detachment, retinal tear, or retinal detachment or required surgery to release traction. CONCLUSION The authors postulate that vitreopapillary traction traumatized disc vessels, causing hemorrhage in and around the disc. The superior hemidisc received the shearing force of detachment, which tore superficial vessels; transmission of the force through the retina caused subretinal bleeding. Posterior vitreous detachment remained incomplete because of tenacious vitreopapillary attachments. Mildly dysplastic discs, as in the young patients with myopia reported here, may have unusual vitreous attachments, predisposing them to the occurrence of and trauma from premature vitreous separation. The condition described is benign and requires no further evaluation or intervention.

Vascular endothelial growth factor and the potential therapeutic use of pegaptanib (Macugen®) in diabetic retinopathy

Both clinical and preclinical findings have implicated vascular endothelial growth factor (VEGF) in the pathophysiology of diabetic macular edema (DME). VEGF is both a potent enhancer of vascular permeability and a key inducer of angiogenesis. VEGF levels are elevated in the eyes of patients with DME, and in animal models of diabetes this elevation coincides with the breakdown of the blood-retinal barrier. Moreover, injection of VEGF (the VEGF165 isoform in particular) into healthy eyes of animals can induce diabetes-associated ocular pathologies.Pegaptanib, a novel RNA aptamer currently used in the treatment of agerelated macular degeneration, binds and inactivates VEGF165 and has been shown in animal models to reverse the blood-retinal barrier breakdown associated with diabetes. These findings formed the basis of a phase II trial involving 172 patients with DME, in which intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections were administered every 6 weeks for 12 weeks, with the option of continuing for 18 more weeks or undergoing laser treatment. Compared to sham, patients receiving 0.3 mg displayed superior visual acuity (p = 0.04) as well as a reduction in retinal thickness of 68 micrometers compared to a slight increase under sham treatment (p = 0.021). These data support the use of pegaptanib in the treatment of DME.

Pain in anterior ischemic optic neuropathy

Purpose The diagnoses of both anterior ischemic optic neuropathy (AION) and optic neuritis are clinical ones with significant overlap of symptoms and signs. This study investigates the presence and character of pain at the onset of AION, in order to evaluate this symptom as a differentiating diagnostic feature between optic neuritis and AION. Methods Forty-one consecutive patients over 45 years of age with a clinical syndrome consistent with AION were questioned about the presence and character of associated pain. Methods Pain was reported by 12% (5 of 41) of the patients with AION. This is contrasted with data compiled on 448 patients enrolled in the optic neuritis treatment trial, of whom 92.2% complained of pain. Methods While there is overlap in the incidence and character of pain in AION and optic neuritis, its presence/absence remains a useful differentiating feature.

Visual function at baseline and 1 month in acute optic neuritis: Predictors of visual outcome

Objective: To identify cutpoints for visual measures at baseline and 1 month predictive of abnormal 6-month vision that could be used as eligibility criteria in a clinical trial to test potential neuroprotection or myelin repair agents in patients with optic neuritis. To determine whether moderate-to-severe dysfunction in one or more visual measures at baseline or 1 month correlates with having major vision loss at 6 months. Methods: We used the Optic Neuritis Treatment Trial database to evaluate various cutpoints for baseline and 1-month vision levels that predicted abnormal 6-month vision. For selected cutpoints, we computed a 95% CI for positive predictive value and the required sample size if the cutpoint was to be used for clinical trial eligibility. We evaluated whether the degree of visual loss at baseline, 1 month, or change in visual function from baseline to 1 month correlated with 6-month visual acuity, contrast sensitivity, or threshold visual field. Results: The best cutpoints for baseline and 1 month were visual acuity ≤ 20/50, contrast sensitivity < 1.0 log units, and visual field mean deviation ≤ −15 dB. The same levels of visual dysfunction at 1 month, but not at baseline, correlated with having 6-month moderate-to-severe loss for each of these measures (p = 0.01). A trial could require as few as 100 subjects for an outcome variable of one or more abnormal measures. Cutpoints at 1 month were highly predictive of abnormal 6-month vision, but the proportion of patients who would be eligible for a trial would be small. Conclusion: Provided data can be used either for the clinician to counsel patients on expected visual outcome or for designing studies to test therapies that might reduce the amount of permanent optic nerve damage due to optic neuritis in high-risk patients.

UPDATE ON NEPHROPATHIC CYSTINOSIS

The cystine that accumulates within cystinotic lysosomes comes primarily from proteins which have been degraded within this organelle. The individual amino acids have specific transport mechanisms to exit the lysosome. The lysosomal cystine transporter is defective in all types of cystinosis. When cells from patients with nephropathic and benign cystinosis were fused, the defect was not corrected and the cystine level remained elevated. This strongly indicates that the genetic defects are allelic (i.e., on the same chromosome). Cysteamine is a weak base which enters the cystinotic lysosome and reacts with cystine forming a mixed disulfide of half-cystine and cysteamine. This mixed disulfide rapidly exits the lysosome via the transport system for cationic amino acids which is normal in cystinosis. Because of the success of renal transplantation, many cystinosis patients are alive in their twenties and even early thirties. Unfortunately, these patients have developed damage to other organs including thyroid, eye, central nervous system, pancreas, and muscle. Cysteamine and its analog, phosphocysteamine, are very beneficial to cystinosis patients, especially when started early in life. These drugs may prevent the need for transplantation. It is too early to know if they will prevent damage to other organs.