Cover Focus | Jan/Feb '16

ME LIVE 2015 Grant Recipients

Dynamic Optical Quality Assessment Using a Double-Pass Wavefront System as Compared to Objective and Subjective Clinical Measures in Dry Eye Disease

Ashley Brundrett, MD, and Michelle Crouse, BA

Purpose: To evaluate the use of optical quality assessment using the double-pass wavefront system to analyze visual function and tear film instability as compared to objective and subjective clinical measures of dry eye disease.

Methods: Prospective study. Patients with dry eye syndrome (DES) diagnosed by symptoms and results of clinical examination, Ocular Surface Disease Index (OSDI), clinical tear break-up time (TBUT), Schirmer’s, and an asymptomatic control group were enrolled in this study. The control group had no ocular surface abnormalities on clinical exam and no complaints of ocular surface symptoms. Optical quality was assessed using the tear film analysis function of the Optical Quality Analysis System (AcuTarget HD/HD Analyzer). Dynamic changes of the Objective Scatter Index (OSI) over 20 seconds were recorded for each patient. Clinical tests and imaging that were performed for comparison were best distance visual acuity (BDVA), manifest refraction, TBUT, corneal staining patterns, Schirmer’s tests, OSDI, and corneal higher order aberrations (HOA) using a Scheimpflug device (Pentacam).

Results: 68 eyes were enrolled in the DES group and 35 eyes in the control group. Mean OSI in DES group was 3.45±3.90 and 2.74±3.43 in the control group (P = .03). Mean OSDI in DES group was 32.89±18.17 and 10.91±8.48 in the control group (P = .02). The DES group was subdivided based on patterns of tear film instability (dynamic OSI graphs), with the two most common being the sawtooth and crescent patterns. Differences were noted within these two groups in OSI, OSDI, and HOA. OSI was 4.54±4.03 in the sawtooth group, compared to an OSI of 2.91±1.85 in the crescent group (P = .03). (Figures 1-3) OSDI was 42.73±17.05 in the crescent group, compared to 32.82±17.63 in the sawtooth group (P = .06). The sawtooth pattern was also correlated with a higher rate of HOA. Both groups exhibit corneal staining abnormalities in similar proportions. Neither group experienced significant decrease in Snellen visual acuity as a result of DES.

Conclusions: Optical quality assessment using the double pass system can be an effective means of evaluating and managing patients with DES, providing an objective measure of disease. Particular patterns of tear film instability may be reflective of severity of patient symptoms and specific clinical findings. In particular, the sawtooth pattern results in a higher OSI, and may be related to presence of HOA, while the crescent pattern leads to greater patient symptoms, as indicated in higher OSDI ratings.

Comparing Refractive Outcomes for Tecnis Multifocal Intraocular Lens Using Various Lens Power Formulae

Wonchon Lin, MD

Purpose: To compare refractive outcomes following Tecnis Multifocal IOL (ZMB00) implantation using Holladay 1, Holladay 2, Hoffer-Q, SRK/T, and the Haigis formula.

Methods: Optical biometry was obtained for 217 eyes from 217 patients who underwent implantation of ZMB00 by the same surgeon (D.R.H). Personalized Haigis constants were obtained from this set of data. The Wang-Koch correction was applied to axial lengths greater than 25.2 mm. The mean absolute error (MAE) between the actual and predicted refractive errors for each formula were calculated. Results were stratified into axial length range cohorts defined as short (<22.0 mm), average (22.0- 24.49 mm), medium long (24.5-25.99 mm) and very long (>26.0 mm).

Results: The MAE for the various formulae was 0.31 for Holladay 1, 0.33 for Holladay 2, 0.37 for Hoffer-Q, 0.33 for SRK/T, and 0.29 for Haigis. For short axial lengths, the MAE for Haigis was less than the other formulae (0.47 vs. 0.61, 0.61, 0.61, 0.68). For average and medium long axial lengths, all the formulae performed similarly. For very long axial lengths, the Haigis (0.258) performed comparably with Holladay 1 (0.254) and SRK/T (0.257) and better than Holladay 2 (0.321) and Hoffer-Q (0.346).

Conclusions: The personalized Haigis formula had the lowest MAE and best overall performance across the entire spectrum of axial lengths. The trends observed for each formula with ZMB00 are similar to those observed in monofocal IOLs, suggesting that the lens formulae do not deviate significantly for multifocal IOLs.

Forward Light Scattering Increases in Keratoconic Eyes

Anthony Leonard, PhD; Scott D. Gardner, MD; Evan R. Zeldin; David M. Tremblay, MD; Karolinne M. Rocha, MD, PhD; and George O. Waring IV, MD, FACS

Purpose: To measure visual quality and quantify forward light scattering in keratoconic eyes.

Methods: Forward light scattering (FLS) was measured in keratoconic eyes and normal eyes using a commercially available double- pass retina point imaging instrument. Objective scattering index (OSI) values were stratified according to keratoconus severity scale (KSS) and Amsler-Krumeich (AK) scores as determined by clinical exam, Placido disc topography, and Scheimpflug tomography.

Results: OSI increased in keratoconic eyes (6.59 ± 1.09 vs. control 0.76 ± 0.52; mean ± SEM), in AK stages 1-4 of keratoconus, and KSS stages 3-4. Receiver-operator characteristic (ROC) curve analysis obtained an area under the curve (AUC) of 0.884 when evaluating OSI as a unimodal diagnostic indicator for any KSS stage and 0.991 for KSS stages 3 and higher. An AUC of 0.938 was obtained in comparing suspect (KSS 1 & 2) versus keratoconic (KSS 3 & 4) eyes. Increasing corneal steepening patterns on tomography were associated with increased broadening of PSF and increased OSI.

Conclusions: Forward light scattering increased in keratoconic eyes, indicating decreased vision quality. This increased scattering as measured by objective scatter index (OSI) was determined to be a sensitive and specific marker for the diagnosis of keratoconus given the large areas under the curve obtained in ROC analysis.

A Novel Spectral Domain Optical Coherence Tomography (SD-OCT) Classification Scheme for the Differential Diagnosis of Macular Edema of Diabetic and Retinal Veno-Occlusive Origin

Mikel Mikhail, MD; Razek Coussa, MD; and David E. Lederer, MD, FRCSC

Purpose: To assess SD-OCT morphologic patterns of macular edema secondary to different disease entities and identify predictors of pathology on OCT.

Methods: 91 eyes of 67 patients with macular edema secondary to diabetic (61 eyes) and veno-occlusive pathologies (30 eyes) were retrospectively examined using Cirrus HD-OCT (Carl Zeiss Meditec). Images were graded according to a number of qualitative and quantitative parameters

Results: Foveal retinal nerve fiber layer (RNFL) thickness, followed by cyst type and central macular thickness were the strongest predictors of pathology. A thicker foveal RNFL, the presence of empty cysts and a greater central macular thickness are the most important predictors of macular edema secondary to retinal veno-occlusive disease. A thinner foveal RNFL, the presence of diffuse speckled cysts, smaller central macular thickness and the presence of sub retinal fluid are more likely to be found in diabetic macular edema. The presence, location and relation of microfoci to cysts were not significantly different between the groups.

Conclusions: Recognition of the characteristic OCT patterns of macular edema allows for disease identification and classification on the basis of OCT alone.

Toxoplasma Gondii Infection Among Hispanics in Southern California: Prevalence and Parasite Strains

Christian Sanfilippo, MD

Purpose: To confirm a high prevalence of Toxoplasma gondii infection among Hispanic individuals in southern California; and to identify factors possibly related to the increased prevalence in this population.

Methods: In this cross-sectional study (2011-12), prevalence of T. gondii infection was determined on the basis of antibodies against SAG1 among southern California Hispanic volunteers without toxoplasmic retinochoroiditis at 3 clinical sites. An ELISA assay identified antibodies against strain-specific T. gondii-associated peptides; people were determined to be infected with Type II or non-Type II strains. The following demographic information was collected from all individuals: sex; age; country of birth; and time spent in the United States, if foreign-born.

Results: T. gondii infection was confirmed in 50 (36.2%) of 138 individuals, 43 (86%) of whom had non-Type II infections. The majority (n = 135, 98.5%) were born outside of the United States. There was no significant difference in age between infected and non-infected subgroups, but infected individuals had spent more time in their home countries before immigration to the US than non-infected individuals (P = .025).

Conclusions: Hispanic immigrants in southern California are more likely to be T. gondii-infected than other demographic groups in the US. Demographic and serologic findings suggest that they were infected in their home countries. High prevalence of T. gondii infection with predominantly non-Type II strains places this population at risk for clinical diseases, such as toxoplasmic retinochoroiditis.

Impact of Combination Glaucoma Therapies on Beta-Blocker Exposure

Kunyong Xu, MD, MHSc

Purpose: Beta-adrenergic receptor antagonists (beta-blockers) used in the treatment of glaucoma are an often-overlooked source of systemic adverse events. Ophthalmic timolol has been associated with severe systemic adverse events including numerous cases resulting in death. In recent years the number of fixed-dose combination therapies for glaucoma has grown rapidly, and among available combination therapies only the non-selective beta-blocker timolol is used as the beta-blocker component.

Methods: A population-based study was conducted in Ontario, Canada between January 1, 2001, and December 31, 2012, to assess the shift to combination therapies in the management of glaucoma, and to investigate the impact of this shift on the relative use of selective and non-selective beta-blockers in patients with this disease.

Results: Between 2001 and 2012 timolol (non-selective beta-blocker) use grew at an average annual rate of 2.2% (P < .0001), while betaxolol (selective beta-blocker) use declined by 14.1% per year (P < .0001). These changes in the relative use of betaxolol and timolol coincided with changes in the relative use of combination and single drug therapies. Over the study period, the use of beta-blockers as single drug therapy decreased 7.7% annually (P < .0001). In contrast, the use of combination therapies containing a beta-blocker increased 7.6% annually (P < .0001).

Conclusions: The introduction of fixed combination glaucoma therapies has been associated with a significant shift to greater use of non-selective beta-blockers. In vulnerable older populations, this may have an important impact on patient safety that warrants further study.

Pupillary Dynamics of Patients on Tamsulosin Exhibiting Intraoperative Floppy Iris Syndrome During Cataract Surgery

Chetra Yean; Bella Wolf; and Anurag Shrivastava, MD

Purpose: To measure the pupillary dynamics of patients on tamsulosin who exhibit intraoperative floppy iris syndrome using the Neuroptics NPi-200, a handheld, digital pupillometer.

Methods: Pupillary dynamics of patients on tamsulosin and control patients who underwent cataract surgery between July 2015 and August 2015 were measured prior to and after dilation for surgery. Measured pupillary dynamics included: resting pupil diameter and subsequent contraction, latency, constriction velocity, and dilation velocity. The operating surgeon, masked to the groups, rated presence and degree of intraoperative floppy iris syndrome.

Results: Eleven eyes of 11 tamsulosin patients and 31 eyes of 31 control patients were included. Mean pre-dilated max diameter for tamsulosin patients was 3.15±0.66, which is 16% smaller than the mean for controls (3.73±0.93, P = .03). Similarly, the mean pre-dilated resting diameter for tamsulosin patients was 2.27±0.37, 16% smaller than the mean for controls (2.70±0.72, P = .01). All other pupillary dynamics were not significantly different between the two groups. Of the 11 tamsulosin patients, 45% (5) exhibited IFIS, ranging from grade 1 to grade 3. No significant differences of pupillary dynamics were found between IFIS and non-IFIS Flomax patients, but mean post-dilated max diameter was approaching significance, with IFIS patients being 17% smaller (5.91±1.16) than non-IFIS cases (7.15±0.93, P = .07). All other pupillary dynamics were not significantly different between the two groups.

Conclusions: The pupillometer measured significant differences in pupillary dynamics between patients on tamsulosin and controls. It also identified differences approaching significance between IFIS patients and non-IFIS patients, specifically post-dilated maximum pupil size. Pupillary dynamics of patients on tamsulosin may be measured prior to surgery to determine if IFIS is likely to occur informing surgeons to use special precautions.

Ocular Light Scatter, Ray-Tracing Aberrometry, and Scheimpflug Densitometry as an Objective Measure of Dysfunctional Lens Syndrome

Evan Zeldin; George O. Waring IV, MD, FACS; Karolinne Rocha, MD, PhD

Purpose: To evaluate the optical quality of the aging crystalline lens using double-pass imaging system, ray-tracing wavefront, and Scheimpflug technologies, and to assess visual function and quality of vision of patients with presbyopia with different degrees of lens opacity.

Methods: Prospective study. The study included presbyopic patients with different degrees of crystalline lens opacity (LOCSIII classification) and a control group of young patients. A double-pass wavefront (AcuTarget HD) was used to measure ocular forward light scattering, specifically the Objective Scatter Index (OSI). Ray-tracing aberrometer (iTrace) was used to analyze ocular internal aberrations and modulation transfer function (MTF) to generate the Dysfunctional Lens Index (DLI). Crystalline lens density was measured using a non-contact rotating Scheimpflug device (Pentacam).

Results: A total of 166 eyes with lens opacity and 82 normal eyes were enrolled in this study. Mean DLI was 6.44 ± 2.553 in the lens opacity group and 8.22 ± 4.179 in the control group (P < .001). Mean OSI in the lens opacity group was 2.88 ± 2.550 and 0.72 ± 0.354 in the control group (P < .001). Mean lens density was 26.80 ± 9.851 GSU in the lens opacity group and 19.19 ± 5.657 GSU in the control group (P < .001).

Conclusions: Objective scatter index and dysfunctional lens index are reliable, objective measures of visual impairment and offer a novel way to quantitatively evaluate visual degradation caused by the aging lens with different degrees of crystalline lens opacification.

Thank you to the grant providers!