Evaluation of a short-term topical interferon α-2b treatment for histologically proven melanoma and primary acquired melanosis with atypia.

OBJECTIVE: To evaluate the efficiency of series of 6-week treatments with brief intervals (6-week = 1 cycle) of topical Interferon α-2b (IFNα-2b) treatment in primary acquired melanosis (PAM) with atypia and melanoma of the conjunctiva. PATIENTS AND METHODS: Five patients with biopsy-proven PAM with atypia and seven patients with melanoma of the conjunctiva, treated with topical IFNα-2b (1 million units/ml, 5 times daily), were included in the study. All patients had colour photographs and the tumour area was measured manually for each patient before and after treatment. RESULTS: The median age of 12 patients at initiation of treatment was 61.5 years (range 39-75 years). The mean therapy duration was 2.4 cycles (range 1-6 cycle). Compared to pretreatment lesion dimension, the mean decrease in tumour size were after the first cycle 66% (range 18-98%; p = 0.004; n = 10 patients), after the second cycle 55% (range 10-100%; p = 0.016; n = 7 patients), and after the third cycle 74% (range 23-100%; n = 3 patients). In one patient 6 cycles of topical IFNα-2b were needed. The decrease in size was 22% after the 4(th) cycle, 34% after the 5(th) cycle, and 98% after the 6(th) cycle. CONCLUSION: Our clinical experience demonstrates promising results of topical IFNα-2b treatment for PAM with atypia and melanoma of the conjunctiva without any local or systemic side effects. However, future multicenter prospective studies are recommended to confirm the efficiency and safety of topical IFNα-2b treatment.

A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy.

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

Uveitis in a patient treated with Bacille-Calmette-Guérin: possible antigenic mimicry of mycobacterial and retinal antigens.

PURPOSE: To investigate the cellular immune response in uveitis developing after intravesical Bacille-Calmette-Guérin (BCG) applications. DESIGN: Experimental study. PARTICIPANTS: A 72-year-old HLA-B27-negative patient with bilateral granulomatous anterior uveitis that developed during the third cycle of intravesical BCG applications she was receiving for treatment of bladder carcinoma. METHODS: The patient's peripheral T cell reactivity to ocular autoantigens was compared with the response to purified protein derivative (PPD) from Mycobacterium tuberculosis. T-cell proliferation and cytokine and chemokine secretion were measured in vitro. MAIN OUTCOME MEASURES: Anterior uveitis was treated successfully with topical corticosteroids and cycloplegics. RESULTS: The following were demonstrated: proliferation to PPD, interphotoreceptor retinoid-binding protein (IRBP), and IRBP-peptide R16, as well as secretion of proinflammatory cytokines in response to PPD, retinal soluble antigen (S-Ag), IRBP, cellular retinal-binding protein (CRALBP), and some S-Ag and IRBP peptides. CONCLUSIONS: These data indicate the generation of a polyclonal autoimmune reaction elicited by BCG. Amino acid sequence alignments revealed homologies between proteins from M. tuberculosis, BCG, and retinal antigens, suggesting antigenic mimicry as a potential cause of uveitis in this patient.

Evaluation of the New "SAVE" Protocol in Diabetic Macular Edema Over the Course of Anti-VEGF Treatment.

BACKGROUND: To evaluate a recently established grading protocol for diabetic macular edema (DME) over the course of intravitreal anti-VEGF treatment with ranibizumab. METHODS: Fluorescein angiography images and optical coherence tomography scans before treatment and after 3 monthly applied intravitreal ranibizumab injections were retrospectively graded for each included study eye according to the recently introduced "SAVE" grading protocol ("S"= subretinal fluid; "A"= "area of retinal thickening"; "V"="vitreo-retinal abnormalities"; "E"="etiology of leakage focal versus non-focal") and correlated with best-corrected visual acuity (BCVA) in letters (lett). RESULTS: Five of the 39 included study eyes had subretinal fluid ("S") before treatment which resolved during treatment. BCVA of study eyes with an initial retinal thickening smaller than one disc diameter ("A") was non-significantly higher compared to patients with a retinal thickening greater than one disc diameter (34.0 ± 17.9 lett versus 25.3 ± 13.3 lett, p=0.236) but became significant during treatment (40.5 ± 10.0 lett versus 28.3 ± 13.1 lett, p=0.004). No difference in BCVA was observed between patients with or without vitreo-retinal abnormalities ("V") before and during therapy. BCVA in patients with focal leakage ("E") was significantly higher than in patients with non-focal leakage before (33.1 ± 12.3 lett versus 23.3 ± 13.3 lett, p=0.017) and during (38.9 ± 10.9 lett versus 26.3 ± 12.6 lett, p=0.002) therapy. CONCLUSIONS: Applying the grading protocol "SAVE", focal leakage ("E") was the only retrospectively observed parameter which significantly correlated with a better BCVA before therapy and over the course of treatment in patients with fovea-involving DME.

Bilateral acute iris transillumination.

OBJECTIVE: To describe a series of patients with bilateral acute iris transillumination, pigment dispersion, and sphincter paralysis. METHODS: We reviewed the medical records and clinical photographs of 26 patients seen at 5 centers in Turkey and Belgium between March 16, 2006, and July 6, 2010. Observation procedures included clinical examination, anterior segment color photography, gonioscopy, laser flare photometry, and pupillometry. RESULTS: All 26 patients (20 women and 6 men; mean [SD] age, 43.2 [10.5] years) had bilateral involvement. Twenty-three patients (88%) had acute-onset disease with severe photophobia and red eyes. Nineteen patients (73%) had a preceding flulike illness and used systemic antibiotics, including moxifloxacin. Diagnostic laboratory workup was unremarkable. There was pigment discharge into the anterior chamber, and flare was elevated in the absence of inflammatory cells. Most patients had severe diffuse transillumination of the iris and mydriatic distorted pupils. Pupillometry revealed a compromised reaction to light. The most serious complication was an intractable early rise in intraocular pressure. Gonioscopy revealed heavy pigment deposition in the trabecular meshwork. Although symptoms were relieved promptly by application of topical corticosteroid, the median duration of pigment dispersion was 5.25 months. CONCLUSIONS: Bilateral acute iris transillumination with pigment dispersion and persistent mydriasis is a new clinical entity that is not an ocular adverse effect of oral moxifloxacin treatment, as previously suggested. The etiopathogenesis of this entity remains to be elucidated.