Author: Ophthalmology

Anatomic Features and Function of the Macula and Outcome of Surgical Tenotomy and Reattachment in Achiasma – Corrected Proof

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Objective:
To examine the anatomic features and function of the macula in achiasma and to compare visual acuity, eye movements, foveation, and eye velocity before and after tenotomy and reattachment (T&R) surgery.

Design:
Case series.

Participants:
Two children with isolated achiasma.

Methods:
Ophthalmologic examinations, brain magnetic resonance imaging, full-field and multifocal electroretinography (ERG), visual evoked potentials (VEPs), spectral-domain optical coherence tomography (OCT), eye-movement recordings, and unilateral T&R in 1 patient.

Main Outcome Measures:
Visual acuity before and after surgery, macular anatomic features and function, and eye velocity before and after T&R surgery in 1 patient.

Results:
Magnetic resonance imaging and VEP confirmed absence of decussation of retinofugal fibers in both patients. Visual acuity was 20/100 and 20/200. The anatomic features and function of the fovea and macula were normal by OCT and multifocal ERG. After T&R, there was a marked reduction in horizontal eye velocity and monocular visual acuity improved to 20/80.

Conclusions:
The finding that the macula is normal in achiasma suggests that reduced acuity is the result of retinal image motion from nystagmus. Two-muscle T&R reduces horizontal retinal image motion and can improve visual acuity in achiasma or patients with infantile nystagmus.

Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Ability of Cirrus High-Definition Spectral-Domain Optical Coherence Tomography Clock-Hour, Deviation, and Thickness Maps in Detecting Photographic Retinal Nerve Fiber Layer Abnormalities – Corrected Proof

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Purpose:
To investigate the ability of clock-hour, deviation, and thickness maps of Cirrus high-definition spectral-domain optical coherence tomography (HD-OCT) in detecting retinal nerve fiber layer (RNFL) defects identified in red-free fundus photographs in eyes with early glaucoma (mean deviation >–6.0 dB).

Design:
Cross-sectional study.

Participants:
Two hundred ninety-five eyes with glaucomatous RNFL defects with clear margins observed in red-free fundus photographs and 200 age-, sex-, and refractive error–matched healthy eyes were enrolled.

Methods:
The width and location of RNFL defects were evaluated by using the red-free fundus photograph. When a RNFL defect detected by red-free fundus photograph did not present as (1) yellow/red codes in the clock-hour map, (2) yellow/red pixels in the deviation map, or (3) blue/black areas in the thickness map, the event was classified as a misidentification of a photographic RNFL defect by Cirrus HD-OCT. In healthy eyes, the presence of false-positive RNFL color codes of Cirrus HD-OCT maps was investigated.

Main Outcome Measures:
The prevalence of and factors associated with the (1) misidentification of photographic RNFL defects by Cirrus HD-OCT in eyes with glaucoma and (2) false-positive RNFL color codes of Cirrus HD-OCT maps in healthy eyes were assessed.

Results:
Among the 295 red-free fundus photographic RNFL defects from 295 eyes with glaucoma, 83 (28.1%), 27 (9.2%), and 0 (0%) defects were misidentified in the clock-hour, deviation, and thickness maps of Cirrus HD-OCT, respectively. Fifty-six defects (19.0%) were misidentified only in the clock-hour map and 27 (9.2%) in both the clock-hour and deviation maps. The misidentification of photographic RNFL defects by Cirrus HD-OCT was associated with a narrower width and a temporal location of RNFL defects (P<0.05). Among the 200 healthy eyes, 25 (12.5%), 30 (15.0%), and 12 (6.0%) eyes had false-positive RNFL color codes in clock-hour, deviation, and thickness maps of Cirrus HD-OCT, respectively.

Conclusions:
Among the clock-hour, deviation, and thickness maps obtained with Cirrus HD-OCT, the thickness map showed the best diagnostic ability in detecting photographic RNFL defects. The RNFL thickness map may be a useful tool for the detection of RNFL defects in eyes with early glaucoma.

Financial Disclosure(s):
The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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Ability of Cirrus High-Definition Spectral-Domain Optical Coherence Tomography Clock-Hour, Deviation, and Thickness Maps in Detecting Photographic Retinal Nerve Fiber Layer Abnormalities – Corrected Proof

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Purpose:
To investigate the ability of clock-hour, deviation, and thickness maps of Cirrus high-definition spectral-domain optical coherence tomography (HD-OCT) in detecting retinal nerve fiber layer (RNFL) defects identified in red-free fundus photographs in eyes with early glaucoma (mean deviation >–6.0 dB).

Design:
Cross-sectional study.

Participants:
Two hundred ninety-five eyes with glaucomatous RNFL defects with clear margins observed in red-free fundus photographs and 200 age-, sex-, and refractive error–matched healthy eyes were enrolled.

Methods:
The width and location of RNFL defects were evaluated by using the red-free fundus photograph. When a RNFL defect detected by red-free fundus photograph did not present as (1) yellow/red codes in the clock-hour map, (2) yellow/red pixels in the deviation map, or (3) blue/black areas in the thickness map, the event was classified as a misidentification of a photographic RNFL defect by Cirrus HD-OCT. In healthy eyes, the presence of false-positive RNFL color codes of Cirrus HD-OCT maps was investigated.

Main Outcome Measures:
The prevalence of and factors associated with the (1) misidentification of photographic RNFL defects by Cirrus HD-OCT in eyes with glaucoma and (2) false-positive RNFL color codes of Cirrus HD-OCT maps in healthy eyes were assessed.

Results:
Among the 295 red-free fundus photographic RNFL defects from 295 eyes with glaucoma, 83 (28.1%), 27 (9.2%), and 0 (0%) defects were misidentified in the clock-hour, deviation, and thickness maps of Cirrus HD-OCT, respectively. Fifty-six defects (19.0%) were misidentified only in the clock-hour map and 27 (9.2%) in both the clock-hour and deviation maps. The misidentification of photographic RNFL defects by Cirrus HD-OCT was associated with a narrower width and a temporal location of RNFL defects (P<0.05). Among the 200 healthy eyes, 25 (12.5%), 30 (15.0%), and 12 (6.0%) eyes had false-positive RNFL color codes in clock-hour, deviation, and thickness maps of Cirrus HD-OCT, respectively.

Conclusions:
Among the clock-hour, deviation, and thickness maps obtained with Cirrus HD-OCT, the thickness map showed the best diagnostic ability in detecting photographic RNFL defects. The RNFL thickness map may be a useful tool for the detection of RNFL defects in eyes with early glaucoma.

Financial Disclosure(s):
The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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Prevalence and 5- to 6-Year Incidence and Progression of Myopia and Hyperopia in Australian Schoolchildren – Corrected Proof

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Purpose:
We sought to determine the prevalence, incidence, and change in refractive errors for Australian schoolchildren and examine the impact of ethnicity and sex.

Design:
Population-based cohort study.

Participants:
The Sydney Adolescent Vascular and Eye Study, a 5- to 6-year follow-up of the Sydney Myopia Study, examined 2760 children in 2 age cohorts, 12 and 17 years. Longitudinal data were available for 870 and 1202 children in the younger and older cohorts, respectively.

Methods:
Children completed a comprehensive examination, including cycloplegic autorefraction (cyclopentolate 1%; Canon RK-F1). Myopia was defined as ≤−0.50 diopters (D) and hyperopia as ≥+2.00 D right eye spherical equivalent refraction.

Main Outcome Measures:
Baseline and follow-up refraction.

Results:
Prevalence of myopia increased between baseline and follow-up for both the younger (1.4%–14.4%; P<0.0001) and older cohorts (13.0%–29.6%; P<0.0001). The annual incidence of myopia was 2.2% in the younger cohort and 4.1% in the older. Children of East Asian ethnicity had a higher annual incidence of myopia (younger 6.9%, older 7.3%) than European Caucasian children (younger 1.3%, older 2.9%; all P<0.0001). The prevalence of myopia in European Caucasian children almost doubled between the older (4.4%; 95% confidence interval [CI], 3.0–5.8) and younger samples (8.6%; 95% CI, 6.7–10.6) when both were aged 12 years. Children with ametropia at baseline were more likely to have a significant shift in refraction (hyperopia: odds ratio [OR], 3.4 [95% CI, 1.2–9.8]; myopia: OR, 6.3 [95% CI, 3.7–10.8]) compared with children with no refractive error. There was no significant difference in myopia progression between children of European Caucasian and East Asian ethnicity (P = 0.7).

Conclusions:
In Sydney, myopia prevalence (14.4%, 29.6%) and incidence (2.2%, 4.1%) was low for both age cohorts, compared with other locations. However, in European Caucasian children at age 12, the significantly higher prevalence of myopia in the younger sample suggests a rise in prevalence, consistent with international trends. Progression of myopia was similar for children of East Asian and European Caucasian ethnicity, but lower than reported in children of East Asian ethnicity in East Asia, suggesting that environmental differences may have some impact on progression.

Financial Disclosure(s):
The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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Quantifying Diplopia with a Questionnaire – Corrected Proof

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Purpose:
To report a diplopia questionnaire (DQ) with a data-driven scoring algorithm.

Design:
Cross-sectional study.

Participants:
To optimize questionnaire scoring, 147 adults with diplopic strabismus completed both the DQ and the Adult Strabismus-20 (AS-20) health-related quality-of-life (HRQOL) questionnaire. To assess test–retest reliability, 117 adults with diplopic strabismus. To assess responsiveness to surgery, 42 adults (46 surgeries).

Methods:
The 10-item AS-20 function subscale score (scored 0–100) was defined as the gold standard for severity. A range of weights was assigned to the responses and the gaze positions (from equal weighting to greater weighting of primary and reading). Combining all response option weights with all gaze position weights yielded 382848 scoring algorithms. We then calculated 382848 Spearman rank correlation coefficients comparing each algorithm with the AS-20 function subscale score.

Main Outcome Measures:
To optimize scoring, Spearman rank correlation coefficients (measuring agreement) between DQ scores and AS-20 function subscale scores. For test–retest reliability, 95% limits of agreement and intraclass correlation coefficient (ICC). For responsiveness, change in DQ score.

Results:
For the 382 848 possible scoring algorithms, correlations with AS-20 function subscale score ranged from −0.64 (best correlated) to −0.55. The best-correlated algorithm had response option weights of 5 for rarely, 50 for sometimes, and 75 for often, and gaze position weights of 40 for straight ahead in the distance, 40 for reading, 1 for up, 8 for down, 4 for right, 4 for left, and 3 for other, totaling 100. There was excellent test–retest reliability with an ICC of 0.89 (95% confidence interval, 0.84–0.92), and 95% limits of agreement were 30.9 points. The DQ score was responsive to surgery with a mean change of 51±34 (P<0.001).

Conclusions:
We have developed a data-driven scoring algorithm for the DQ, rating diplopia symptoms from 0 to 100. On the basis of correlations with HRQOL, straight-ahead and reading positions should be highly weighted. The DQ has excellent test–retest reliability and responsiveness, and may be useful in both clinical and research settings.

Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Enhanced Depth Imaging Optical Coherence Tomography of Optic Nerve Head Drusen – Corrected Proof

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Objective:
To assess the value of enhanced depth imaging optical coherence tomography (EDI OCT) in diagnosing and evaluating optic nerve head drusen (ONHD) compared with conventional diagnostic methods.

Design:
Prospective, comparative, cross-sectional study.

Participants:
Thirty-four patients with clinically visible or suspected ONHD in either eye based on dilated optic disc examination or optic disc stereophotography and without ocular comorbidity.

Methods:
Spectral-domain OCT of the optic nerve head in both conventional (non-EDI) and EDI modes, ultrasound B-scan, and standard automated perimetry were performed on both eyes of all participants.

Main Outcome Measures:
Detection and findings of ONHD between EDI OCT and conventional diagnostic methods.

Results:
Sixty-eight eyes were clinically classified into 3 groups: 32 eyes with definite ONHD, 25 eyes with suspected ONHD, and 11 normal-appearing fellow eyes. In the definite ONHD group, EDI OCT, non–EDI OCT, and ultrasound B-scan were positive for ONHD in all eyes and visual field (VF) was abnormal in 24 eyes. In the suspected ONHD group, EDI OCT, non–EDI OCT, ultrasound B-scan, and VF were positive in 17, 14, 7, and 3 eyes, respectively; 8 eyes had no evidence of ONHD in any of the tests. In normal-appearing fellow eyes, EDI OCT, non–EDI OCT, ultrasound B-scan, and VF were positive in 3, 1, 1, and 0 eyes, respectively; 4 eyes had no evidence of ONHD in any of the tests. Enhanced depth imaging OCT had a significantly higher ONHD detection rate than ultrasound B-scan in all eyes (52/68 eyes vs. 40/68 eyes; P<0.001), in eyes with clinically suspected ONHD or normal-appearing fellow eyes (20/36 eyes vs. 8/36 eyes; P<0.001), and in eyes with clinically suspected ONHD (17/25 eyes vs. 7/25 eyes; P = 0.002). Enhanced depth imaging OCT–detected ONHD appeared as signal-poor regions surrounded by short, hyper-reflective bands or isolated/clustered hyper-reflective bands without a signal-poor core. In non–EDI OCT, posterior surfaces of the ONHD and deep-seated hyper-reflective bands were invisible or less clear than in EDI OCT.

Conclusions:
Enhanced depth imaging OCT detects lesions likely representing ONHD more often and better assesses their shape and structure than conventional tests.

Financial Disclosure(s):
Proprietary or commercial disclosure may be found after the references.

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Immunologic Graft Rejection in Descemet’s Stripping Endothelial Keratoplasty and Penetrating Keratoplasty for Endothelial Disease – Corrected Proof

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Objective:
To evaluate and compare the cumulative incidence and risk factors for first-episode immunologic graft rejection in Descemet’s stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) and to identify potential risk factors for rejection.

Design:
Retrospective chart review.

Participants:
All patients who underwent PK or DSAEK for endothelial disease at the Department of Ophthalmology, North Shore LIJ, between January 2004 and June 2010.

Methods:
One hundred sixty-nine PK cases and 122 DSAEK cases were reviewed. All patients had a minimum of 3 months of follow-up, with median follow-up of 36 months in the PK group and 29 months in the DSAEK group.

Main Outcome Measures:
Cumulative incidence of first-episode immunologic graft rejection in PK and DSAEK cohorts. Risk factors for graft rejection were reviewed.

Results:
Cumulative incidence of rejection was not significantly different between the DSAEK and PK cohorts (P<0.1324). However, among patients without glaucoma, the risk of rejection in PK was higher than that in DSAEK (hazard ratio [HR], 5.56). Prior incisional glaucoma surgery imparted a 3.15 times greater risk of rejection regardless of transplant type. Phakic patients were more likely to experience rejection than patients with a posterior chamber intraocular lens (HR, 3.23; P<0.0266), but not more likely than those with an anterior chamber intraocular lens or who were aphakic. Graft failure occurred within 6 months in 31% of PK rejections and none of the DSAEK rejections.

Conclusions:
Descemet’s stripping automated endothelial keratoplasty and PK did not show a statistically significant difference in the incidence of rejection; however, among nonglaucomatous eyes, there were significantly fewer rejections in those that underwent DSAEK.

Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Ophthalmic Evaluations in Clinical Studies of Fingolimod (FTY720) in Multiple Sclerosis – Corrected Proof

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Purpose:
To report outcomes of ophthalmic evaluations in clinical studies of patients receiving fingolimod (Gilenya; Novartis Pharma AG, Basel, Switzerland) for multiple sclerosis (MS).

Design:
Analysis done on pooled safety data (N = 2615, all studies group) from 3 double-masked, randomized, parallel-group clinical trials (phase 2 core and extension >5 years, and phase 3 FREEDOMS and TRANSFORMS core and extension studies).

Participants:
Patients aged 18 to 55 years (18–60 years in phase 2 study) diagnosed with relapsing-remitting MS were included. Patients with diabetes mellitus or macular edema (ME) at screening were excluded.

Intervention:
Participants received fingolimod (0.5/1.25 mg), placebo, or interferon beta for the respective study durations. Ophthalmic examination included detailed eye history (at screening), visual acuity (VA) assessment, dilated ophthalmoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA).

Main Outcome Measures:
Extensive ophthalmic monitoring was performed for all patients. While being studied, patients with abnormal findings on dilated ophthalmoscopy and OCT compatible with ME were further studied by FA. All locally diagnosed ME cases were centrally reviewed by the retina specialist (M.A.Z.) on the Data and Safety Monitoring Board.

Results:
Among 2615 patients assessed, 19 confirmed ME cases were observed in fingolimod-treated groups (0.5 mg: n = 4, 0.3%; 1.25 mg: n = 15, 1.2%). Most patients (n = 13, 68%) presented with blurred vision, decreased VA, or eye pain. Macular edema was diagnosed within 3 to 4 months of treatment initiation in most cases (n = 13, 68%); 2 patients had late onset (>12 months) ME. Of the 19 patients with ME, 5 (26%), all treated with fingolimod 1.25 mg, had a history of uveitis compared with 26 (1%) in the all studies group. In most cases (n = 16, 84%), ME resolved after discontinuing the study drug. Eleven patients required topical anti-inflammatory medications. No patient had further vision deterioration.

Conclusions:
Fingolimod 0.5 mg is associated with a low incidence of ME in MS studies. Patients with a history of uveitis may be at an increased risk of developing ME. An ophthalmic examination before initiating fingolimod therapy and regular follow-up eye examinations during fingolimod therapy are recommended.

Financial Disclosure(s):
Proprietary or commercial disclosure may be found after the references.

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Inclusion of Genotype with Fundus Phenotype Improves Accuracy of Predicting Choroidal Neovascularization and Geographic Atrophy – Corrected Proof

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Purpose:
The accuracy of predicting conversion from early-stage age-related macular degeneration (AMD) to the advanced stages of choroidal neovascularization (CNV) or geographic atrophy (GA) was evaluated to determine whether inclusion of clinically relevant genetic markers improved accuracy beyond prediction using phenotypic risk factors alone.

Design:
Cohort study.

Participants:
White, non-Hispanic subjects participating in the Age-Related Eye Disease Study (AREDS) sponsored by the National Eye Institute consented to provide a genetic specimen. Of 2415 DNA specimens available, 940 were from disease-free subjects and 1475 were from subjects with early or intermediate AMD.

Methods:
DNA specimens from study subjects were genotyped for 14 single nucleotide polymorphisms (SNPs) in genes shown previously to associate with CNV: ARMS2, CFH, C3, C2, FB, CFHR4, CFHR5, and F13B. Clinical demographics and established disease associations, including age, sex, smoking status, body mass index (BMI), AREDS treatment category, and educational level, were evaluated. Four multivariate logistic models (phenotype; genotype; phenotype + genotype; and phenotype + genotype + demographic + environmental factors) were tested using 2 end points (CNV, GA). Models were fitted using Cox proportional hazards regression to use time-to-disease onset data.

Main Outcome Measures:
Brier score (measure of accuracy) was used to identify the model with the lowest prediction error in the training set. The most accurate model was subjected to independent statistical validation, and final model performance was described using area under the receiver operator curve (AUC) or C-statistic.

Results:
The CNV prediction models that combined genotype with phenotype with or without age and smoking revealed superior performance (C-statistic = 0.96) compared with the phenotype model based on the simplified severity scale and the presence of CNV in the nonstudy eye (C-statistic = 0.89; P<0.01). For GA, the model that combined genotype with phenotype demonstrated the highest performance (AUC = 0.94). Smoking status and ARMS2 genotype had less of an impact on the prediction of GA compared with CNV.

Conclusions:
Inclusion of genotype assessment improves CNV prediction beyond that achievable with phenotype alone and may improve patient management. Separate assessments should be used to predict progression to CNV and GA because genetic markers and smoking status do not equally predict both end points.

Financial Disclosure(s):
Proprietary or commercial disclosure may be found after the references.

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