PurposeRetinal detachment (RD) separates the retina from the underlying retinal pigment epithelium, resulting in a gradual degeneration of photoreceptor (PR) cells. It is known that RD also results in an inflammatory response, but its contribution to PR degeneration is unknown. In this study we examine the inflammatory responses to RD in patient vitreous and validate a mouse experimental RD as a model of this phenomenon.MethodsMultiplex bead arrays were used to examine cytokine levels in vitreous samples from 24 patients with macula-off rhegmatogenous retinal detachment (RRD) undergoing reattachment surgery and from 10 control patients undergoing vitrectomy for vitreous opacities or epiretinal membrane. Activation of the innate immune response was then examined in a mouse model of RD.ResultsTwenty-eight factors were significantly increased in vitreous from RD patients versus controls. Notable were the cytokines MCP-1 (CCL2), IP-10 (CXCL10), fractalkine (CX3CL1), GRO (CXCL1), MDC (CCL22), IL-6, and IL-8, which all exhibited relatively high concentrations and several-fold increases in the vitreous of RD patients. Concentrations of various analytes correlated with a range of clinical variables such as duration of detachment and visual acuity. Retinal detachment in the mouse resulted in cytokine mRNA expression changes consistent with human RD vitreous results, as well as microglial proliferation and migration toward the outer retina.ConclusionsThe findings suggest that an inflammatory response involving microglia is a component of the reaction to retinal detachment that may impact visual acuity after surgical repair and that mouse experimental RD can serve as a model to study this effect.

Previously, we used mass spectrometry to demonstrate pheromone-stimulated phosphorylation of Ser-539 in Sst2, a regulator of G protein signaling in yeast Saccharomyces cerevisiae [Garrison, T. R., et al. (1999) J. Biol. Chem. 274, 36387-36391]. Here, we show that Sst2 phosphorylation is mediated by the mitogen-activated protein (MAP) kinase Fus3. Phosphorylation occurs within a canonical MAP kinase phosphorylation site (Pro-X-Ser/Thr-Pro, where "X" at the -1 position can be any amino acid), a consensus sequence deduced earlier from analysis of synthetic peptide substrates. In a direct test of the model, we compared Sst2 phosphorylation following systematic substitution of the -1 residue His-538. Each of the substitution mutants was suitable as a MAP kinase substrate, as shown by phosphorylation-dependent mobility shifts in vivo and/or by direct phosphorylation in vitro followed by peptide mapping and mass spectrometry sequencing. This analysis documents phosphorylation of Sst2 by Fus3 and demonstrates that the prevailing model for MAP kinase recognition is valid for a native substrate protein in vivo as well as for small synthetic peptides tested in vitro.

PurposeTo evaluate if projection-resolved optical coherence tomographic angiography (PR-OCTA) reduces projection artifact with less attenuation of choroidal neovascularization (CNV) flow signal compared to conventional OCTA with slab subtraction.MethodsIn this retrospective cross-sectional study, participants with subfoveal treatment-naïve CNV secondary to age-related macular degeneration underwent OCTA. Scans were exported for custom processing including manual segmentation as necessary, application of slab subtraction and PR-OCTA algorithm, and calculation of CNV vascular area and connectivity. CNV was classified as type 1, minimally type 2, or predominantly type 2 based on fluorescein angiography (FA) and OCT. Two masked retina specialists independently classified CNV using cross-sectional conventional OCTA and PR-OCTA.ResultsA total of 17 eyes were enrolled in this study. Mean CNV vessel area (mm2) was 0.67 ± 0.51 for PR-OCTA and 0.53 ± 0.41 for slab subtraction (P = 0.018). Mean vascular connectivity was 96.80 ± 1.28 for PR-OCTA and 90.90 ± 4.42 (P = 0.018) for slab subtraction. Within-visit repeatability (coefficient of variation) of PR-OCTA was 0.044 for CNV vessel area and 0.012 for vascular connectivity, compared to 0.093 and 0.028 by slab subtraction. PR-OCTA classification agreement with FA/OCT was 88.2% and 76.5% for the two graders, while conventional OCTA agreement was 58.8% and 70.6% (grader 1, P = 0.025; grader 2, P = 0.56). Moreover, PR-OCTA enabled the individual quantification of type 1 and type 2 components of a CNV.ConclusionsPR-OCTA had greater CNV vessel area and vascular connectivity, as well as better repeatability, compared to slab subtraction, suggesting PR-OCTA is a superior technique for imaging CNV. Furthermore, PR-OCTA removes projection artifact on cross-sectional OCTA, improving the ability to classify and quantify CNV components.

BackgroundStandard upper blepharoplasty involves removal of both the skin and a portion of the underlying orbicularis oculi muscle. The senior author had observed sluggishness of eyelid closure, lagophthalmos as well as varying degrees of eye irritation in certain patients during the early postoperative period. He postulated that these findings could be due to orbicularis muscle excision. He therefore undertook a prospective study 27 years ago comparing standard blepharoplasty on one eyelid to skin-only excision on the fellow eyelid.MethodsA randomized, prospective, single-blinded study was designed using the fellow eye as an internal control. 22 patients undergoing upper blepharoplasty procedure requiring greater than 5 mm of skin resection and with no history of ophthalmologic disease, dry eye, or previous eyelid surgery were selected. Upper blepharoplasty was performed with skin-only removal on one side, and combined skin-muscle removal on the other side. Patients were evaluated until six months after surgery except for two patients who were lost to follow-up after three months. Sluggish eyelid closure, lagophthalmos, dry eye and aesthetic result were outcome measures scored by patient survey, the operating surgeon, and a blinded expert panel.ResultsThere were comparable aesthetic outcomes in both eyelids. The incidence of sluggish eyelid closure, lagophthalmos and dry eye syndrome were significantly higher in eyelids where wide segments of muscle had been resected.ConclusionsMuscle-sparing upper blepharoplasty produces similar aesthetic outcomes as conventional blepharoplasty, while significantly reducing the complications of sluggish eyelid closure, lagophthalmos and dry eye disease. The authors therefore recommend muscle-sparing upper blepharoplasty.