Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or “wet” form of AMD, no therapy is successful for the non-neovascular or “dry” form. Here we discuss the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments. In our view, these should emphasize system biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.

Purpose: To investigate elevated intraocular pressures (IOP) (defined by a measurement >25 mmHg at a follow-up visit) after an intravitreal injection of anti-vascular endothelial growth factor agents for age-related macular degeneration. Methods: Retrospective review of medical records. Results: A total of 127 patients (155 eyes) received an intravitreal injection of anti-vascular endothelial growth factor agents (bevacizumab, ranibizumab, or pegaptanib) ranging from 1 to 39 injections for more than a period of 30 to 1759 days. Among this population, 12 patients (14 eyes; 9.4%) developed elevated IOP >25 mmHg. Of these, 7 patients (5.5%) developed sustained elevated IOP (IOP >25 mmHg on 2 separate visits requiring glaucoma medication or surgery), of which 8 eyes required topical medications and 1 eye underwent glaucoma surgery. Mean IOP of injected eyes receiving intravitreal injection was 15.2 ± 2.4 mmHg, and the mean IOP was 14.9 ± 2.6 mmHg for noninjected eyes. Among eyes that had elevated IOPs, there was no association with injection frequency, number of injections, or anti-vascular endothelial growth factor agent used. Conclusion: Elevated IOP, sustained or unsustained, after intravitreal injection is not uncommon. No association with patient demographics or injection history was identified in the authors' study population.

Age-related maculopathy (ARM) is a common cause of visual impairment in the elderly populations of industrialized countries and significantly affects the quality of life of those suffering from the disease. Variants within two genes, the complement factor H (CFH) and the poorly characterized LOC387715 (ARMS2), are widely recognized as ARM risk factors. CFH is important in regulation of the alternative complement pathway suggesting this pathway is involved in ARM pathogenesis. Two other complement pathway genes, the closely linked complement component receptor (C2) and complement factor B (CFB), were recently shown to harbor variants associated with ARM. We investigated two SNPs in C2 and two in CFB in independent case-control and family cohorts of white subjects and found rs547154, an intronic SNP in C2, to be significantly associated with ARM in both our case-control (P-value 0.00007) and family data (P-value 0.00001). Logistic regression analysis suggested that accounting for the effect at this locus significantly (P-value 0.002) improves the fit of a genetic risk model of CFH and LOC387715 effects only. Modeling with the generalized multifactor dimensionality reduction method showed that adding C2 to the two-factor model of CFH and LOC387715 increases the sensitivity (from 63% to 73%). However, the balanced accuracy increases only from 71% to 72%, and the specificity decreases from 80% to 72%. C2/CFB significantly influences AMD susceptibility and although accounting for effects at this locus does not dramatically increase the overall accuracy of the genetic risk model, the improvement over the CFH-LOC387715 model is statistically significant.

Case Report from JAMA Ophthalmology — Acetazolamide in the Treatment of X-Linked Retinoschisis Maculopathy

Research from JAMA Ophthalmology — A Clinician's View of the Molecular Genetics of Age-Related Maculopathy