Small et al (p. 9) set out to identify specific mutations causing North Carolina macular dystrophy (NCMD). They identified 5 rare mutations, each of which is capable of arresting the development of the human macula. Four of the mutations strongly implicate the involvement of the gene PRDM13 in macular development, and although the pathophysiologic mechanism of the fifth remains unknown, it may involve the developmental dysregulation of IRX1. For this study, the researchers performed whole genome sequencing coupled with analysis of gene expression in human retinal cells.

We read with great interest the recent paper by Kwon et al1 in which the authors examine the aqueous levels of cytokines in patients with diabetic eye disease, including angiopoietin-like 4 (ANGPTL4), a protein we and others have identified as an important vascular hyperpermeability factor in cancer.2 We were pleased to see the authors corroborate our recent study in which we first identified ANGPTL4 as an important player in the promotion of macular edema in patients with ischemic retinal disease, including diabetic macular edema.

The article by Crama and Klevering (see p. 32) makes important observations about significant long-term complications of hydrogel episcleral implants (MIRAgel; MIRA, Inc., Waltham, MA) used as scleral buckles in 467 eyes. This is the largest series reported of the complications of MIRAgel implants and illustrates how these implants swell slowly, eventually creating orbital masses, extraocular motility disorders, buckle exposure, and intraocular complications. The enlargement of the MIRAgel scleral buckle increased progressively, so patients did not experience problems until 5 to 10 years after their retinal detachment repair.

We read with interest the article by Mehta et al1 on vitreous evaluation. We were impressed and intrigued by the large number of vitreous samples evaluated by cytopathology from the 3 institutions. The authors described negative biopsy reports for malignancy from 5736 vitreous samples. The rationale for subjecting vitreous samples from therapeutic vitrectomies to cytopathology by Tufts Medical Center and Boston Medical Center begs further explanation, because most centers do not routinely practice vitreous sampling for vitrectomies related to vitreous hemorrhage and cases such as the removal of lens fragments, lens capsule, and internal limiting membrane.