Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: a 36-month pilot study

The adenosine antagonist 7-methylxanthine (7-mx) works against myopia in animal models. In a clinical trial, 68 myopic children (mean age 11.3 years) received either placebo or 7-mx tablets for 12 months. All participants subsequently received 7-mx for another 12 months, after which treatment was stopped. Axial length was measured with Zeiss IOL-Master and cycloplegic refraction with Nikon Retinomax at −6, 0, 12, 24, and 36 months. Axial growth was reduced among children treated with 7-mx for 24 months compared with those only treated for the last 12 months. Myopia progression and axial eye growth slowed down in periods with 7-mx treatment, but when the treatment was stopped, both myopia progression and axial eye growth continued with invariable speed. The results indicate that 7-mx reduces eye elongation and myopia progression in childhood myopia. The treatment is safe and without side effects and may be continued until 18–20 years of age when myopia progression normally stops

Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial

Background: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel. Objective: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). Methods: 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial with scanning laser polarimetry (GDx) at 6 month as a primary outcome measure, optical coherence tomography (OCT), visual and electrophysiological secondary outcome measures. Participants aged 18­55 years, ≤ 28 days of onset of first episode unilateral ON, were randomised to amiloride (10mg daily for 5 months) or placebo. (clinicaltrials.gov, NCT 01802489) Results: ITT cohort consisted of 43 patients; 23 placebo, and 20 amiloride. No significant drug related adverse events occurred.No significant differences were found in GDx (p=0.840). Visual evoked potentials were significantly prolonged in the amiloride group compared to placebo (p=0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. Conclusion: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm but future neuroprotective trials in ON should target the window of opportunity to maximize potential neuroprotective benefit.</p

Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial

Background: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel. Objective: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON). Methods: 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial with scanning laser polarimetry (GDx) at 6 month as a primary outcome measure, optical coherence tomography (OCT), visual and electrophysiological secondary outcome measures. Participants aged 18andshy;55 years, andle; 28 days of onset of first episode unilateral ON, were randomised to amiloride (10mg daily for 5 months) or placebo. (clinicaltrials.gov, NCT 01802489) Results: ITT cohort consisted of 43 patients; 23 placebo, and 20 amiloride. No significant drug related adverse events occurred.No significant differences were found in GDx (p=0.840). Visual evoked potentials were significantly prolonged in the amiloride group compared to placebo (p=0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer. Conclusion: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm but future neuroprotective trials in ON should target the window of opportunity to maximize potential neuroprotective benefit.</p

Visual acuity after retinal gene therapy for Choroideremia

Two recent clinical reports of retinal gene therapy with adeno-associated virus (AAV) vectors in patients with Leber’s congenital amaurosis showed initial gains in visual function that subsequently declined. We previously reported early improvement in visual acuity in two of six patients who received retinal gene therapy in one eye (the study eye) to treat choroideremia, a disease that is characterized by atrophy of the choriocapillaris and retinal pigment epithelium and involves vision loss that leads to blindness

GABAergic agents modify the response of chick scleral fibroblasts to myopic and hyperopic eye cup tissues

Purpose: GABA antagonists inhibit experimental myopia in chick and GABA receptors have been localized to chick sclera and the retinal pigment epithelium (RPE). The RPE and the choroid alter scleral DNA and glycosaminoglycan (GAG) content in vitro; opposite effects have been observed for tissues from myopic and hyperopic eyes. The aim was to determine the effect of GABAergic agents on the DNA and GAG content of chick scleral fibroblasts directly and in co-culture with ocular tissues from myopic and hyperopic chick eyes. Materials and Methods: Primary cultures of fibroblastic cells expressing vimentin and α-smooth muscle actin were established. GABAergic agents were added separately (i) to the culture medium of the scleral cells and (ii) to the culture medium of the scleral cells with the addition of posterior eye cup tissue (retina, RPE, retina + RPE, choroid + RPE) to cell culture inserts. Ocular tissues were obtained from chick eyes wearing + 15D (lens-induced hyperopia, LIH) or −15D lenses (lens-induced myopia, LIM) for three days (post-hatch day 5–8) (n = 12). GAG and DNA content of scleral fibroblasts were measured. Results: GABA agents had a small direct effect on scleral cell GAG and DNA content but a larger effect was measured when GABA agents were added to the culture medium with myopic and hyperopic RPE and choroid + RPE tissues. GABA agonists increased (p = 0.002) whereas antagonists decreased (p = 0.0004) DNA content of scleral cells; effects were opposite for scleral GAG content. GABA agents significantly altered the effect of both LIM and LIH tissues (p = 0.0005) compared to control; the effects were greater for LIM tissue versus LIH tissue co-culture (p = 0.0004). Conclusion: GABAergic agents affect the DNA and GAG content of scleral fibroblasts both directly and when co-cultured with ocular tissues. GABA antagonists that prevent myopia development in chick model could act via a scleral mechanism utilizing the RPE/choroid