Molecular genetics of inherited retinal degenerations in Icelandic patients.

The study objective was to delineate the genetics of inherited retinal degenerations (IRDs) in Iceland, a small nation of 364.000 and a genetic isolate. Benefits include delineating novel pathogenic genetic variants and defining genetically homogenous patients as potential investigative molecular therapy candidates. The study sample comprised patients with IRD in Iceland ascertained through national centralized genetic and ophthalmological services at Landspitali, a national social support institute, and the Icelandic patient association. Information on patients' disease, syndrome, and genetic testing was collected in a clinical registry. Variants were reevaluated according to ACMG/AMP guidelines. Overall, 140 IRD patients were identified (point prevalence of 1/2.600), of which 70 patients had a genetic evaluation where two-thirds had an identified genetic cause. Thirteen disease genes were found in patients with retinitis pigmentosa, with the RLBP1 gene most common (n = 4). The c.1073 + 5G > A variant in the PRPF31 gene was homozygous in two RP patients. All tested patients with X-linked retinoschisis (XLRS) had the same possibly unique RS1 pathogenic variant, c.441G > A (p.Trp147X). Pathologic variants and genes for IRDs in Iceland did not resemble those described in ancestral North-Western European nations. Four variants were reclassified as likely pathogenic. One novel pathogenic variant defined a genetically homogenous XLRS patient group.

Population-based incidence of exudative age-related macular degeneration and ranibizumab treatment load.

BACKGROUND/AIMS: The use of intravitreal vascular endothelial growth factor antibodies for exudative age-related macular degeneration (AMD) has stressed ophthalmology services and drug budgets throughout the world. The authors study the population-based incidence of exudative AMD in Iceland and the use of intravitreal ranibizumab in a defined population. METHODS: This is a prospective study of 439 consecutive patients aged 60 years and older with exudative AMD starting intravitreal ranibizumab for exudative AMD in Iceland from March 2007 to December 2009. All patients initially received three consecutive ranibizumab injections, with regular follow-up visits and re-treatment as needed. RESULTS: In total, 517 eyes from 439 patients received treatment for exudative AMD (mean age 79 years). The annual incidence of exudative AMD in the population 60 years and older is 0.29%. The incidence increased with advancing age, double for patients 85 years and older compared with those 75-79 years. Approximately 2400 ranibizumab injections per 100,000 persons aged 60 years and older were given each year for exudative AMD. CONCLUSIONS: These data allow an estimation of the incidence of exudative AMD in a Caucasian population and the treatment load with ranibizumab, which may help plan anti-vascular endothelial growth factor treatment programmes and estimate costs.

Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits.

PURPOSE: This study aimed to develop low-viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits. METHODS: Aqueous eyedrops with hydroxypropyl-beta-cyclodextrin containing 0.01-2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments +/- standard error of the mean) are expressed as the change from baseline (24.7 +/- 3.3 mmHg). RESULTS: Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf-life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 +/- 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 +/- 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10-22 hours after administration and duration of up to 32 hours. CONCLUSIONS: Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low-viscosity aqueous eyedrop formulations.