Intra-population differences of apolipoproteins in the aqueous humor.

BACKGROUND: Evidence suggests that proteins related to lipid metabolism, such as apolipoproteins, play an important role in the maintenance of normal vision. While several members of the apolipoprotein family are abundant in human aqueous humor (AH), their study remains difficult due to the AH's small volume, low protein concentration, and the invasive nature of sample collection. In this study, we report the use of Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to discover associations between AH apolipoproteins and race, gender, and ocular structure in patients with and without primary open angle glaucoma (POAG). METHODS: AH samples were collected from 231 patients undergoing phacoemulsification or glaucoma incisional surgery at the Medical College of Georgia, Augusta University and subsequently analyzed via LC-MS/MS. The number of peptide spectrum matches (PSMs) for each protein was used as a semi-quantitative measure of relative protein levels. Parameters related to ocular structure were determined using Optical Coherence Tomography (OCT) and Heidelberg Retinal Tomography (HRT). These data sets were probed for relationships between apolipoprotein levels and POAG, demographics (gender and race), and ocular structure. RESULTS: A total of ten apolipoproteins were detected in the 231 collected AH samples, with six detected in 100% of the samples, one detected in almost 57% of the samples and three detected in less than 10% of the samples. The levels of APOA1, APOC3, and APOD were higher among POAG subjects. Stratification by gender and race revealed demographic-specific variations. The levels of five apolipoproteins (APOA1, APOA2, APOA4, APOC3, and APOD) were higher in female POAG patients, whereas no apolipoprotein levels were altered in male POAG patients. The levels of APOA1, APOA2, APOA4, and APOD were increased in glaucomatous African American patients, whereas APOE and APOH levels were decreased in glaucomatous Caucasian patients. We also found distinct associations between apolipoprotein levels and OCT and HRT parameters in patients with and without POAG. CONCLUSIONS: The intra-population variation in apolipoprotein levels highlights the heterogeneity of glaucoma as a disease, suggesting the importance of personalized treatments. Gender and race-specific alterations may be associated with higher risks of POAG in females and members of the African American population.

The Constitutive Proteome of Human Aqueous Humor and Race Specific Alterations.

Aqueous humor (AH) is the fluid in the anterior and posterior chambers of the eye that contains proteins regulating ocular homeostasis. Analysis of aqueous humor proteome is challenging, mainly due to low sample volume and protein concentration. In this study, by utilizing state of the art technology, we performed Liquid-Chromatography Mass spectrometry (LC-MS/MS) analysis of 88 aqueous humor samples from subjects undergoing cataract surgery. A total of 2263 unique proteins were identified, which were sub-divided into four categories that were based on their detection in the number of samples: High (n = 152), Medium (n = 91), Low (n = 128), and Rare (n = 1892). A total of 243 proteins detected in at least 50% of the samples were considered as the constitutive proteome of human aqueous humor. The biological processes and pathways enriched in the AH proteins mainly include vesicle mediated transport, acute phase response signaling, LXR/RXR activation, complement system, and secretion. The enriched molecular functions are endopeptidase activity, and various binding functions, such as protein binding, lipid binding, and ion binding. Additionally, this study provides a novel insight into race specific differences in the AH proteome. A total of six proteins were upregulated, and five proteins were downregulated in African American subjects as compared to Caucasians.

Proteomic Alterations in Aqueous Humor From Patients With Primary Open Angle Glaucoma.

Purpose: Primary open angle glaucoma (POAG) is the most prevalent form of glaucoma, accounting for approximately 90% of all cases. The aqueous humor (AH), a biological fluid in the anterior and posterior chambers of the eye, is involved in a multitude of functions including the maintenance of IOP and ocular homeostasis. This fluid is very close to the pathologic site and is also known to have a significant role in glaucoma pathogenesis. The purpose of this study was to identify proteomic alterations in AH from patients with POAG. Methods: AH samples were extracted from 47 patients undergoing cataract surgery (controls: n = 32; POAG: n = 15). Proteomic analysis of the digested samples was accomplished by liquid-chromatography-mass spectrometry. The identified proteins were evaluated using a variety of statistical and bioinformatics methods. Results: A total of 33 proteins were significantly altered in POAG subjects compared with the controls. The most abundant proteins in POAG subjects are IGKC (13.56-fold), ITIH4 (4.1-fold), APOC3 (3.36-fold), IDH3A (3.11-fold), LOC105369216 (2.98-fold). SERPINF2 (2.94-fold), NPC2 (2.88-fold), SUCLG2 (2.70-fold), KIAA0100 (2.29-fold), CNOT4 (2.23-fold), AQP4 (2.11-fold), COL18A1 (2.08-fold), NWD1 (2.07-fold), and TMEM120B (2.06-fold). A significant increasing trend in the odds ratios of having POAG was observed with increased levels of these proteins. Conclusion: Proteins identified in this study are implicated in signaling, glycosylation, immune response, molecular transport, and lipid metabolism. The identified candidate proteins may be potential biomarkers associated with POAG development and may lead to more insight in understanding the mechanisms underlying the pathogenesis of this disease.

Keratoconus unmasked by unilateral ptosis repair.

Astigmatic changes have been shown to occur after ptosis repair due to the altered vector forces on the underlying cornea from the repositioned upper eyelid. The astigmatic change is usually transient, but it may affect a patient's vision for at least the first few months after surgery. The authors present a case of a patient who underwent ptosis repair and subsequently developed postoperative decline in best-corrected visual acuity due to previously undiagnosed keratoconus. The patient's irregular astigmatism seems to have been masked by the ptotic upper eyelid, which we postulate to have acted similar to a stenopaic slit. Correction of the upper eyelid ptosis unveiled previously asymptomatic irregular astigmatism including vertical coma, leading to alteration in the optical wavefront and resultant image degradation.

Virtual reality in ophthalmology training.

Current training models are limited by an unstructured curriculum, financial costs, human costs, and time constraints. With the newly mandated resident surgical competency, training programs are struggling to find viable methods of assessing and documenting the surgical skills of trainees. Virtual-reality technologies have been used for decades in flight simulation to train and assess competency, and there has been a recent push in surgical specialties to incorporate virtual-reality simulation into residency programs. These efforts have culminated in an FDA-approved carotid stenting simulator. What role virtual reality will play in the evolution of ophthalmology surgical curriculum is uncertain. The current apprentice system has served the art of surgery for over 100 years, and we foresee virtual reality working synergistically with our current curriculum modalities to streamline and enhance the resident's learning experience.

Decreased incidence of epithelial defects during laser in situ keratomileusis using intraoperative nonpreserved carboxymethylcellulose sodium 0.5% solution.

PURPOSE: To evaluate the incidence of epithelial defects that occur with laser in situ keratomileusis (LASIK) using nonpreserved carboxymethylcellulose sodium 0.5% solution (Refresh Plus(R)) intraoperatively. SETTING: Community-based refractive center. METHODS: This retrospective study comprised 105 patients (210 eyes) who had primary bilateral LASIK by 1 of 2 surgeons between October 1 and December 1, 2000. The 114 eyes treated subsequent to November 1, 2000, received Refresh Plus intraoperatively, and the 96 eyes treated before this date did not. The incidence of epithelial defects and diffuse lamellar keratitis (DLK) in both groups was recorded. The preoperative keratometry measurements of all cases were also recorded. RESULTS: There was a statistically significant decrease in the incidence of epithelial defects in the group that received Refresh Plus intraoperatively (P =.02). No statistically significant between-group difference in the incidence of DLK was detected. Analysis of the keratometry measurements revealed no statistically significant association between the amount or axis of astigmatism and the incidence of epithelial defects or DLK. CONCLUSION: The intraoperative use of nonpreserved Refresh Plus significantly decreased the rate of epithelial defects that occurred during LASIK.

Diffuse lamellar keratitis associated with carboxymethylcellulose sodium 1% after laser in situ keratomileusis.

PURPOSE: To investigate the association between the use of carboxymethylcellulose sodium 1% (Celluvisc) (Allergan, Inc.) during laser in situ keratomileusis (LASIK) and the development of diffuse lamellar keratitis (DLK). SETTING: Outpatient surgery center, Detroit, Michigan, USA. METHODS: In this retrospective case series, the postoperative clinical course and surgical outcomes in 30 eyes of 15 consecutive patients who had LASIK with the use of Celluvisc were reviewed. All patients had primary LASIK, and the incidence and severity of DLK were analyzed. RESULTS: Diffuse lamellar keratitis developed in 24 of the 30 eyes (80.0%) in which Celluvisc was used before the keratectomy (P = <.0001, Fischer exact test). Sixteen eyes (66.7%) had stage 1, and 8 (33.3%) had stage 2. Diffuse lamellar keratitis was diagnosed in most cases (91.6%) on postoperative day 1. All inflammation resolved after treatment with intense topical corticosteroids. CONCLUSIONS: Celluvisc used immediately before the keratectomy in LASIK was highly associated with the development of DLK.