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Cover Focus | Jan/Feb '17

The Standouts

Eliza Barnwell | Medical University of South Carolina

Analysis of Pseudoaccommodation in Different Intraocular Lens Profiles Using Ray-Tracing Aberrometry and Double-Pass Wavefront

Purpose: To evaluate depth of focus curves and serial measurements of dynamic changes of higher-order aberrations using ray-tracing.

Methods: Dynamic wavefront measurements were performed in normal young subjects and pseudophakic eyes implanted with different.

Results: Dynamic wavefront analyses were performed using ray-tracing and double-pass wavefront. The neutral aspheric IOL (aberration-free) group had better DCNVA and increased pseudoaccommodative range compared to the negative aspheric IOL group (DoF 1.64±1.07 D versus 1.26±0.67 D).

Conclusions: Pseudoaccommodation from changes in spherical aberration, pupil size, and increased depth of focus may contribute to near vision functionality observed in pseudophakic eyes. Ray-tracing and double-pass wavefront analysis explains specific IOLs behavior and its effects in the optical system.

Ashley Brissette, MD | Weill Cornell Medical College

Assessing the Prevalence of Abnormal Tear Testing in Cataract Surgery Patients Using Two Point-of-Care Diagnostic Tests: A Prospective Observational Study

Purpose: Ocular surface disease (OSD) can significantly impact preoperative measurements for cataract surgery. The purpose of this study is to assess the prevalence of abnormal tear testing in preoperative cataract surgery patients using two common point-of-care diagnostic tests and to assess the correlation between patient symptoms and objective test results.

Methods: A prospective observational study of 25 consecutive preoperative cataract surgery patients was conducted. This is an ongoing study with an expected final enrollment of at least 50 patients. Patients with visually significant cataract were included for study at their preoperative appointment. They were administered two ocular surface disease questionnaires: the Ocular Surface Disease Index (OSDI) and the Symptom Assessment in Dry Eye (SANDE) questionnaire. All patients then underwent tear osmolarity testing (TearLab) and matrix metalloproteinase-9 (MMP-9) testing (InflammaDry) regardless of symptomatology and before the instillation of any drops or other testing. Primary outcome measures included tear film osmolarity, tear MMP-9 level, and symptom questionnaire scores.

Results: At least one abnormal tear test was present in 76% of patients, while 40% of patients were abnormal for both tear tests. Sixteen percent of patients had abnormal tear osmolarity (-308 mOsm/L or intereye difference -8 mOsm/L) but were negative for MMP-9. An abnormal MMP-9 and normal osmolarity was found in 20% of patients, and in 24% of patients both tests were normal. OSDI and SANDE symptom scores were well correlated (r=0.55, P=.004). However, there was no statistically significant association between OSDI scores (severe symptoms >33) and abnormal tear osmolarity (P=.29) or MMP-9 (P=.35). SANDE scores (severe symptoms >50) also showed no significant association with osmolarity (P=.28) or MMP-9 levels (P=.13). Mean OSDI and SANDE scores were similar between the subgroup of patients with two abnormal tear tests (36.89 ±29.16 and 31.57 ±31.09) and the subgroup that tested normal for both tear tests (34.97 ±27.71 and 39.05 ±34.65).

Conclusions: There is a high prevalence of OSD in patients who present for cataract surgery as measured by point-of-care diagnostic tear tests. It is well known that signs and symptoms of OSD are often poorly correlated, and this study shows a similarly poor correlation between symptoms and diagnostic tear testing results. In fact, the subgroup that tested normal for both tear tests had the highest mean SANDE symptom score. The poor association between tear tests and patient symptoms suggests that symptomatology alone may miss many affected patients. OSD of any severity level can lead to adverse outcomes in cataract and refractive surgery. Point-of-care diagnostic testing may be useful in identifying early or asymptomatic OSD in preoperative cataract surgery patients, thereby improving refractive outcomes.

Guadalupe Villarreal Jr, MD | Wilmer Eye Institute

AMPK Activator A-769662 Establishes a Corneal Endothelial Protective Phenotype in Normal Human and Fuchs Endothelial Cells

Purpose: Adenosine monophosphate-activated protein kinase (AMPK) is a highly conserved kinase that functions as central node for energy metabolism and intracellular homeostasis. In this study, we examine the expression of the AMPK heterotrimeric complex in the human corneal endothelium and explore its role in the regulation of antioxidant transcriptional programs.

Methods: AMPK subunit expression in normal immortalized human corneal endothelial cells (HCECi) was examined by immunoblot analysis. HCECi and immortalized human Fuchs corneal endothelial cells (FECDi) were treated with a small molecule, direct AMPK activator A-769662. Changes in the mRNA levels of the anti-oxidant transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) and its target genes heme oxygenase 1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase 1 (NQO1) were assessed by real-time quantitative PCR.

Results: The AMPK heterotrimeric complex is expressed in immortalized normal human corneal endothelial cells. Incubation of HCECi with the AMPK activator A-769662 resulted in a significant upregulation of mRNA levels of NRF2 and its downstream anti-oxidant target genes, HO-1 and NQO1. A significant induction of HO-1 and NQO1 expression was also observed in FECDi cells.

Conclusions: Collectively, our data identify the AMPK activator A-769662 as a potentially important regulator of anti-oxidant gene expression in normal and Fuchs human corneal endothelial cells, and suggest that pharmacological activation of AMPK may serve as a novel therapeutic approach for the treatment of FECD.

*Coauthors: Tetsuya Toyono, MD, PhD; Ula V. Jurkunas, MD; Laura Kallay, PhD; and Albert S. Jun, MD, PhD

Joshua Frenkel, MD | Tulane University

Comparison in Biometry of a New Swept-Source Optical Coherence Tomography-Based Biometer Versus Partial Coherence

Purpose: To estimate the repeatability of biometric parameters obtained with a new swept-source biometer and to compare the agreement with that of partial coherence interferometry (PCI) and corneal Scheimpflug-based corneal analyzer.

Methods: Biometry was taken with the use of two different biometers: the IOLMaster 700 swept-source biometer, the partial-coherence interferometry/corneal Scheimpflug-based AL-Scan. Axial length (AL), anterior chamber depth (ACD), corneal power (in diopters [D]), keratometry (K), corneal astigmatism, central corneal thickness (CCT), and lens thickness (LT) between swept-source and PCI-Scheimpflug-based biometry. The repeatability of swept-source biometry was evaluated on the basis of three measurements captured for each patient.

Results: Two hundred twenty cataract eyes were included in the study. The mean difference between swept-source and PCI biometry for AL or ACD, did not show a statistically significant difference (R2=0.9912 and R2=0.9244, respectively). On the contrary, the PCI/corneal Scheimpflug measured a lower mean K value (-0.11 D; P=.01). The mean calculated vector cylinder difference between swept-source and PCI / corneal Scheimpflug-based biometry for keratometry measurements was 0.39 D/2o clockwise rotation when compared to the 2.4 mm optical zone.

Conclusions: Swept-source and PCI/Scheimpflug-based biometry, respectively showed high repeatability performance for all biometric parameters. The agreement of AL, and ACD, swept-source and PCI/Scheimpflug biometry as well as that of CCT between swept-source and PCI/Scheimpflug biometry was very good. A correction factor for K value is noted when comparing the two technologies. It remains to be validated whether high repeatability shown by swept-source or PCI/Scheimpflug biometry will result in improved refractive outcomes.

*Coauthor: Jonathan Solomon; Setting: Bowie Vision Institute, Bowie, Maryland

Rahul Tonk, MD | Bascom Palmer Eye Institute

Tear Film Lipid Layer Thickness in Meibomian Gland Dysfunction

Purpose: To evaluate the correlation between tear film lipid layer thickness (LLT) and signs/symptoms of dry eye disease.

Methods: Single-center, cross-sectional study of 11 eyes in 11 patients presenting with dry eye (mean age, 57.8, range 30-80). Patients completed the Standard Patient Evaluation of Eye Dryness (SPEED), had tear osmolarity and LLT measured, and had meibomian glands imaged. Schirmer I, tear break up time (TBUT), staining, and meibomian gland dysfunction (MGD) grade were recorded.

Results: LLT was negatively correlated with SPEED score (R2=.48, P=.02) and MGD grade (R2 = 0.56, P<.01). MGD grade was positively correlated with gland dropout (R2=0.42, P=.03). SPEED score was also correlated with increased staining (R2=0.40, P=.04), but not with TBUT, Schirmer I, or tear osmolarity.

Conclusion: Laser interferometry for LLT may help predict severity of dry eye symptoms and MGD. LLT may correlate better with dry eye symptoms than some other objective clinical tests for dry eye disease.

Comments: With the growing clinical availability of laser interferometry (Lipiview II, TearScience) as an adjunct diagnostic test for dry eye disease, further research is warranted on lipid layer thickness and signs and symptoms of dry eye. In this cross-sectional study of 11 eyes, laser interferometry measurement of tear film lipid layer thickness correlated well with symptoms of dry eye disease and signs of meibomian gland dysfunction.